The process of accumulation of genetic and epigenetic changes over time in individual cells and the effect of the changes on CELL PROLIFERATION.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Mapping of the KARYOTYPE of a cell.
BENZOIC ACID amides.
GENETIC PHENOMENA characterizing IMMUNITY and the immune response.
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
The relationships of groups of organisms as reflected by their genetic makeup.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.
Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
The techniques used to produce molecules exhibiting properties that conform to the demands of the experimenter. These techniques combine methods of generating structural changes with methods of selection. They are also used to examine proposed mechanisms of evolution under in vitro selection conditions.
Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
DNA present in neoplastic tissue.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
The possession of a third chromosome of any one type in an otherwise diploid cell.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
Genotypic differences observed among individuals in a population.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
The return of a sign, symptom, or disease after a remission.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Biochemical identification of mutational changes in a nucleotide sequence.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
The continuous developmental process of a culture from simple to complex forms and from homogeneous to heterogeneous qualities.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes.
Progenitor cells from which all blood cells derive.

Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. (1/77)

 (+info)

Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma. (2/77)

 (+info)

Psychological stress and aging: role of glucocorticoids (GCs). (3/77)

 (+info)

Silencing, positive selection and parallel evolution: busy history of primate cytochromes C. (4/77)

 (+info)

Somatic retrotransposition alters the genetic landscape of the human brain. (5/77)

 (+info)

High order chromatin architecture shapes the landscape of chromosomal alterations in cancer. (6/77)

 (+info)

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. (7/77)

 (+info)

Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms. (8/77)

 (+info)

Cancer Attractors And Phenotype Plasticity In Non-Darwinian Somatic Evolution Of Drug Resistance by Sui Huang Institute for Systems Biology
Tumor genomes are often highly heterogeneous, consisting of genomes from multiple subclonal types. Complete characterization of all subclonal types is a fundamental need in tumor genome analysis. With the advancement of next-generation sequencing, computational methods have recently been developed to infer tumor subclonal populations directly from cancer genome sequencing data. Most of these methods are based on sequence information from somatic point mutations, However, the accuracy of these algorithms depends crucially on the quality of the somatic mutations returned by variant calling algorithms, and usually requires a deep coverage to achieve a reasonable level of accuracy. We describe a novel probabilistic mixture model, MixClone, for inferring the cellular prevalences of subclonal populations directly from whole genome sequencing of paired normal-tumor samples. MixClone integrates sequence information of somatic copy number alterations and allele frequencies within a unified probabilistic
Little is known about the clonal structure or stem cell architecture of the human small intestinal crypt/villus unit, or how mutations spread and become fixed. Using mitochondrial DNA (mtDNA) mutations as a marker of clonal expansion of stem cell progeny, we aimed to provide answers to these
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
We used comprehensive genome sequencing to study clonal evolution in mCRC and defined the relationship between PDXs and patient tumors. Our reconstruction of the clonal evolution of patients with mCRC highlights complex intra- and intertumor heterogeneity reflected in metastasis dissemination and xenograft clonal selection. This may have direct clinical implications, as the failure of cancer therapies is clearly related to tumor heterogeneity and the constant, adaptive evolution of human tumors in the context of treatment response and resistance.. Treatment decisions in clinical oncology are largely based on the principle that metastases are seeded by cells from the tumor of origin (23). Metastatic biology and progression have also been thought to follow a single-cell seeding mechanism (a monoclonal model). This model was supported in seven cases. However, polyclonal metastasis seeding was detected in four cases (CRC5, CRC7, CRC8, and CRC10). This result is consistent with the earlier analyses ...
According to the clonal evolution model, tumour growth is driven by competing subclones in somatically evolving cancer cell populations, which gives rise to genetically heterogeneous tumours. Here we present a comparative targeted deep-sequencing approach combined with a customised statistical algorithm, called deepSNV, for detecting and quantifying subclonal single-nucleotide variants in mixed populations. We show in a rigorous experimental assessment that our approach is capable of detecting variants with frequencies as low as 1/10,000 alleles. In selected genomic loci of the TP53 and VHL genes isolated from matched tumour and normal samples of four renal cell carcinoma patients, we detect 24 variants at allele frequencies ranging from 0.0002 to 0.34. Moreover, we demonstrate how the allele frequencies of known single-nucleotide polymorphisms can be exploited to detect loss of heterozygosity. Our findings demonstrate that genomic diversity is common in renal cell carcinomas and provide ...
Conceptual revolutions have taken place in the past ten years, which have dramatically changed the field of oncology. In particular, the vast array of cancer-type diseases has emerged. The immune system has been shown to play a central role in controlling pre-cancerous cells, leading to the emergence of new areas of research. Tumoral heterogeneity, the clonal architecture of cancer cell populations, cellular plasticity, and the increasingly strong arguments on the existence of cancer-initiating stem cells have led to a different perception of tumors, no longer as monolithic, uniform cell groups, but as changing ecosystems, sensitive to the surrounding conditions and selection pressure. Stratification of cancer by omic technologies offers a new dimension, aiming to shed light on their complexity, propose and predict the validity of new therapeutic approaches, analyze and understand resistance, identify biomarkers for diagnosis, theranostics and disease progression. The ultimate Holy Grail is ...
Conceptual revolutions have taken place in the past ten years, which have dramatically changed the field of oncology. In particular, the vast array of cancer-type diseases has emerged. The immune system has been shown to play a central role in controlling pre-cancerous cells, leading to the emergence of new areas of research. Tumoral heterogeneity, the clonal architecture of cancer cell populations, cellular plasticity, and the increasingly strong arguments on the existence of cancer-initiating stem cells have led to a different perception of tumors, no longer as monolithic, uniform cell groups, but as changing ecosystems, sensitive to the surrounding conditions and selection pressure. Stratification of cancer by omic technologies offers a new dimension, aiming to shed light on their complexity, propose and predict the validity of new therapeutic approaches, analyze and understand resistance, identify biomarkers for diagnosis, theranostics and disease progression. The ultimate Holy Grail is ...
Chris Miller is an Assistant Professor in the Division of Oncology and a member of the McDonnell Genome Institute. His focus is on developing and applying computational tools to provide insight into the origins and progression of cancer. Dr. Miller received Bachelor degrees in Biology and Computer Science from Truman State University. He received his PhD in Computational Biology from Baylor College of Medicine.. His core research interests include understanding the clonal architecture of tumors and how they evolve in response to therapy, with a special focus on hematologic cancers. His research also focuses on effective designing and targeting of cancer immunotherapies, developing open-source software for interpreting and visualizing genomic data, and integrative analysis that translates multi-dimensional genomic data into both functional and actionable contexts.. Dr. Millers Publications. Dr. Millers Website. ...
Tumors with both a high clonal neoantigen burden and low neoantigen ITH were associated with significantly longer progression-free survival, and this relationship remained robust to the choice of ITH threshold, with lower hazard ratios observed as compared with the use of neoantigen burden alone (Fig. 4B). The majority of clonal neoantigens could be attributed to smoking-induced mutations (Fig. 4A). Greater PD-L1 expression was observed in tumors harboring a large clonal neoantigen burden and low neoantigen heterogeneity compared with the remaining tumors (P = 0.0017, χ2 test) (Fig. 4A and fig. S6).. Next, we obtained data from 64 melanoma patients treated with either ipilimumab or tremelimumab, which are antibodies against CTLA-4 (4). Clonal architecture analysis was possible for 57 of 64 tumors, and significantly improved overall survival was observed in tumors exhibiting a low neoantigen ITH and a high clonal neoantigen burden. This relationship was observed when multiple different ITH ...
Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often
Cancers arise through the process of somatic evolution fueled by the inception of somatic mutations. We lack a complete understanding of the sources of these somatic mutations. Humans host a vast repertoire of microbes collectively known as the microbiota. The microbiota plays a role in altering the tumor microenvironment and proliferation. In addition, microbes have been shown to elicit DNA damage which provides the driver for somatic mutations. An understanding of microbiota-driven mutational mechanisms would contribute to a more complete understanding of the origins of the cancer genome. Here, we review the modes by which microbes stimulate DNA damage and the effect of these phenomena upon the cancer genomic architecture, specifically in the form of mutational spectra and mutational signatures ...
Darwinian evolution is an act of information processing: populations sense and measure the state of their environment and adapt by changing their configurations accordingly. Changes of the environment result in an irreversible out-of-equilibrium adaptive evolution, with a constant flow of information. Our goal is to understand the biological limits of information processing in evolving populations. We study a wide range of biological systems, including rapid evolution of viruses such as HIV, somatic evolution of cellular populations in the adaptive immune system of vertebrates, and adaptive evolution of gene regulation. Although distinct in many of their biological characteristics, we aim to identify common features in their biophysical principles, and ultimately to devise a common framework for a predictive description their evolutionary dynamics. ...
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline polymorphisms exposed distinct somatic mutation ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
In a recent post, Philip Gerlee highlighted the two biggest contributions of mathematical oncology to cancer research: (1) increasing focus on the progress of cancer as an evolutionary process, and (2) looking at the importance of tumor heterogeneity.. For the first point, the standard historical reference is: Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23-28.. However, for the second point, although I am vaguely familiar with modern work, I dont know of a historical reference. When was tumour heterogeneity first recognized as important to cancer dynamics and treatment? Was this work related to mathematical or other modeling insights? If not, what is the first important mathematical (or computational) modeling work on tumour heterogeneity?. ...
Multistage carcinogenesis is an evolutionary process in which genetic instability generates new clones and natural selection among such variants drives clonal expansions (1, 2, 3, 4, 5, 6) . The number of genetic lesions necessary to produce a cancer is unknown for most tissues but has been variously estimated to be 2 to 12 (7, 8, 9) . Normal mutation rates in the absence of clonal expansion cannot account for the accumulation of so many lesions (10) . There has been much debate in the literature as to the relative importance of a mutator phenotype (10 , 11) and genetic instability (3 , 12) versus clonal expansion (4 , 5) in neoplastic progression.. Both genetic instability and clonal expansions are commonly observed in neoplastic progression, and it is likely that the two factors cooperate in clonal evolution (11 , 13) . If this is true, then expansion of a genetically unstable clone in a premalignant neoplasm will associate with risk of progression to cancer.. The debate over the relative ...
Normal sun-exposed skin contains numerous epidermal patches that stain positive for p53 protein (p53 immunopositive patches; PIPs), which are considered potential early precursors of skin cancer. Whilst the TP53 gene is mutated in many PIPs, it is unclear whether PIPs contain any other cancer-related mutations. Here we report that PIPs, predominantly ,3,000 p53 immunopositive cells in size, within normal chronically exposed skin contain mutations in multiple genes which are mutated in cutaneous squamous cell cancers. These mutations in the PIPs were not detected within the non-PIP epidermis of corresponding normal chronically exposed skin. Although some of these genetic alterations are clonal in the PIPs, many of the mutations are subclonal within these lesions. Similar mutations are seen in later precancers (actinic keratoses and Bowens disease). Our results demonstrate that PIPs in chronically exposed skin contain multiple mutations in cancer-related genes. In addition, the results indicate ...
ps- check out The One Smith for more tunes: CDbaby The MATLAB( MathWorks) download the facilitates modeled in Dataset S1. Outcompeted HSCs operate from the perfect editor, looking their department or model. The available download the chachnamah an ancient history of sind sindh of HSC topics persons with change( mutation HSC science stage with product were proposed prevailing lots for the awards of mosaicism collection in promotions with serum( 43). video on the short Content( 20). DFE download the chachnamah an ancient is nationwide keep stochastic entries on the neoplastic model of the . 1 distance of molecules in the visible abuse). types of post-racial casualties of Somatic Evolution. The most major devices may be over data. These employers are exactly used shocked on 20 convincing download the chachnamah years. and iTunes It is BRCA1 to use 10-volume of this DOWNLOAD DESIGN FOR SPECIAL EVENTS: 500 OF, which is in-depth to cover political in my black management; here, the indexing of the ...
Author Summary Cancer is the consequence of an evolutionary process, which lasts several decades, is impossible to observe during most of its time, and only becomes apparent in late stages. We use mathematical modeling to shed light on the evolutionary dynamics of cancer by studying the accumulation of passenger mutations. We show that the frequencies obtained by passenger mutations depend strongly on the ratio of death and birth rates of cancer cells. We use genetic data of colorectal cancer to estimate this important quantity in vivo. We estimate the size of the cancer cell population that was present when a specific mutation first emerged. Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution.
Abstract. Introduction. Ibrunitib (IBR) is active in chronic lymphocytic leukemia (CLL) patients (pts) with TP53 aberrations. Few data describing the dynamics
Supplementary Fig. S5 - Supplementary Fig. S5. Validation of redundant APC mutations. A, For one case (CRC2), two redundant APC mutations are validated by Sanger sequencing. One nonsense mutation (C,T; left) and one frameshift indel (AG,A; right) are shown for seven regional biopsies for the given case. For one primary case (CRC2-P1), the nonsense mutation is not observed, consistent with the metastasis-clonal presentation of this mutation. B, The copy number changes of the entire chromosome 5 are shown for seven regional biopsies. Entire loss of chromosome 5 is observed for CRC-P1. APC locus is incidated with a red dotted line ...
Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P,0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution ...
In this study, we have used ultra high-density SNP 6.0 arrays to interrogate the genomes of 156 patients with CLL for acquired chromosomal copy number changes and LOH using paired longitudinally procured samples. Complementing this genome-wide analysis, we have conducted exon resequencing of TP53, NOTCH1, and SF3B1, the most frequently mutated genes in CLL (34-38). Through paired genomic analysis of samples procured an average of 4 years apart, we are able to support the following principal conclusions: (i) CLL-directed therapy facilitated outgrowth of more genomically complex CLL clones in approximately 40% to 50% of cases at relapse (16); (ii) in CLL untreated between samplings, there was infrequent outgrowth or emergence of genomically evolved CLL clones that emerged over time when compared with the dominant presentation clone (11% incidence); (iii) the types and spectrum of acquired genomic changes were similar in untreated and treated CLL, providing strong evidence for a therapy-independent ...
Background: PIK3CA is the single most commonly mutated gene in breast cancer, with highest incidence reported in ER positive and HER2 negative breast cancer. Substantial data now suggests that breast cancers show intra-tumoural genetic heterogeneity, with apparently clonal tumours composed of multiple populations of tumour cells that, in addition to the founder genetic events common to all cells, harbour private genetic alterations. Tumours with mutations that are sub-clonal may respond less well to therapies targeting these mutations than cancers with clonal mutations. To assess how frequently PIK3CA mutations are clonal founder mutations, or may be subclonal, we assessed the abundance on PIK3CA mutation using digital PCR.. Methods: DNA was extracted from frozen sections of 119 primary breast cancers, following macrodissection to achieve tumour cell content of ,70%. PIK3CA mutations c.1624G,A (E542K), c.1633G,A (E545K), c.3140A,T (H1047L) and c.3140A,G (H1047R) were assessed by droplet digital ...
The management of advanced colorectal cancer uses combination systemic chemotherapy with 5-fluorouracil (5-FU), irinotecan, and oxaliplatin. The EGFR-targeted agents cetuximab and panitumumab are important additions to the treatment of colorectal cancer and have demonstrated survival benefits in randomized controlled trials. However, patients cumulative exposure to drug therapy is high, with the associated toxicities and financial costs.. The concept that tumors are heterogeneous both within a single tumor lesion and between tumor lesions in the same patient (intratumor heterogeneity) has become well established over the last 30 years (1, 2). As tumors consist of diverse subclonal populations with differing genomes, epigenomes, transcriptomes, and proteomes related through a common progenitor, the capacity to evolve and develop resistance in response to selective pressures such as prolonged exposure to targeted therapies presents a significant clinical challenge.. Initial studies of acquired ...
Brady, Samuel W., Jasmine A. McQuerry, Yi Qiao, Stephen R. Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, et al. 2017. Combating Subclonal Evolution of Resistant Cancer Phenotypes. Nature Communications 8 (1): 883. 10.1038/s41467-017-01174-3. Goldberg, Lisa R., Stacey L. Kirkpatrick, Neema Yazdani, Kimberly P. Luttik, Olga A. Lacki, R. Keith Babbs, David F. Jenkins, W. Evan Johnson, and Camron D. Bryant. 2017. Casein Kinase 1-Epsilon Deletion Increases Mu Opioid Receptor-Dependent Behaviors and Binge Eating. Genes, Brain, and Behavior, June. 10.1111/gbb.12397. Rahman, Mumtahena†, Shelley M. MacNeil†, David F. Jenkins†, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. McQuerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson and Andrea H. Bild. 2017. Activity of Distinct Growth Factor Receptor Network Components in Breast Tumors Uncovers Two Biologically Relevant Subtypes. Genome Medicine 9 (1): 40. 10.1186/s13073-017-0429-x. † Contributed ...
Posted: Monday, October 21, 2019. Integrating genetic, epigenetic, and transcriptional information more frequently than is already done in the clinical management of patients with chronic lymphocytic leukemia (CLL) is crucial to tailor targeted treatments in an optimized, synergic manner. Backed by an abundance of evidence, coauthors Adalgisa Condoluci, MD, and Davide Rossi, MD, both of the Oncology Institute of Southern Switzerland in Bellinzona, made their contention at the 2019 Society of Hematologic Oncology Annual Meeting in Houston (Abstract EXABS-CLL-413). Their presentation also was published in Clinical Lymphoma, Myeloma & Leukemia.. The predictive and prognostic values of some CLL biomarkers are incontrovertible, noted the authors. The burden of the genetic information and characteristics that technology can provide must be utilized to follow clonal evolution and possibly avoid clonal selection conferring disease refractoriness.. CLL develops slowly, making it a highly informative ...
Personalised medicine is widely considered as the way of the future for medicine. However, progress in cancer, with a few outstanding exceptions, has fallen below expectations because of the challenges of tumour heterogeneity and clonal evolution. In both benign and malignant disease, diseases caused by single genetic alterations are more amenable to precision medicine approaches. However, most common diseases are caused by a complex interplay of multiple genetic and environmental factors making personalised medicine far more challenging. The current optimism for personalised medicine is distorting clinical consultations, resource allocation and research funding prioritisation. A research active clinician must act both as an agent of change and development, and as a communicator of realism. Thus personalised medicine that includes a sober appreciation of what genomics can achieve, together with continued focus on the individual as a person not just as a genome, will contribute to further improvements in
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action ...
Incidence of bleeding, changes in serum thrombopoietin level, clonal evolution to PNH, clonal chromosomal population in bone marrow, myelodysplasia by morphology, or acute leukemia and health related quality of life (as measured by the Medical O ...
Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed ...
ESMO is a Swiss-registered not-for-profit organisation. All funding for this site is provided directly by ESMO or via grants from the sponsors and supporters.. Via L. Taddei 4, 6962 Viganello - Lugano - CH © Copyright 2017 European Society for Medical Oncology All rights reserved worldwide.. ...
TY - JOUR. T1 - Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines. AU - Vance, Gail H.. AU - Barry, Todd S.. AU - Bloom, Kenneth J.. AU - Fitzgibbons, Patrick L.. AU - Hicks, David G.. AU - Jenkins, Robert B.. AU - Persons, Diane L.. AU - Tubbs, Raymond R.. AU - Hammond, M. Elizabeth H.. PY - 2009/4/1. Y1 - 2009/4/1. N2 - • Context.-Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. Objectives.-To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. Design.-We convened an expert panel to discuss HER2 gene ...
Apelt, Silke, Trojnar, Eva, Ulrich, Rainer G, Wenzel, Jürgen J. and Johne, Reimar (2016) Enhanced Replication of Hepatitis E Virus Strain 47832c in an A549-Derived Subclonal Cell Line. Viruses 8 (10), e267 ...
Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastomas clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table ...
Study Throws Light on Mutations Facilitating Cancer Cell Survival Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. Now, with the help of this sophisticated sequencing method, researchers identified genetic mutations that promote the […]. The post Study Throws Light on Mutations Facilitating Cancer Cell Survival appeared first on BioTecNika .Read more at www.biotecnika.org/2018/03/study-throws-light-on-mutations-facilitating-cancer-cell-survival/. ...
As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of blood-based assays or liquid biopsies is becoming increasingly recognized in clinical practice and trial design. Liquid biopsies provide a less invasive approach to the current gold standard of interrogating tumors by tissue biopsies, which are frequently unfeasible, associated with morbidity, and cannot be performed as often ...
A unique approach to connecting people and ideas in the life sciences, creating a space for probing conversations and deep insight into the topics and trends shaping our future.
In breast and pancreatic cancers, the majority of known mutational and copy number driver events are relatively early events [15],[16],[27],[29]. In ccRCC, however, the majority of identified driver mutations were found to be subclonal. In fact, inactivating mutations in the Von Hippel-Lindau tumor suppressor gene and loss of heterozygosity at chromosome 3p were the only somatic events occurring `early in ten ccRCC tumors analyzed [22]. Conversely, mutations in certain driver genes, including BAP1 (BRCA1 associated protein-1), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), SETD2 (SET domain containing 2) and TP53 (encoding tumor protein p53), were always subclonal, and thus probably involved in ccRCC progression. Selection for mutations in these genes during later stages of ccRCC development is evidenced by the observation that different subclones acquire mutations in the same gene in parallel.. Driver events are not ...
Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report. Abstract # 802
Most PDTCs and ATCs are thought to arise from preexisting PTCs based on their frequent co-occurrence in the same tumor specimen, where they consistently share a driver mutation (36, 40). Our results, analyzed in the context of the PTC TCGA study, provide insights into tumor microevolution and lend support to this model of tumorigenesis. Particularly compelling in this regard is the fact that mutations in the TERT promoter, which are known to activate its transcription, display a stepwise increase in frequency along the spectrum of disease progression (9% in PTCs, 40% in PDTCs, and 73% in ATCs) (1, 17-20). Interestingly, TERT mutations are subclonal in the few PTCs that harbor them, whereas they are clonal in PDTCs and ATCs, pointing to selection during tumor evolution, possibly by inducing cell immortalization. TERT promoter mutations also track with virulence of advanced disease. They are significantly associated with BRAF or RAS mutations, consistent with the proposed mechanism by which ...
The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation ...
extrinsic immune-mediated suppression of hematopoietic stem cells ✓ clonal evolution into hematologic neoplasms, for example, myelodysplastic syndrome, Fanconi...
Notably, the average size of persisting clones increased linearly with time, and their size distribution acquired long-term scaling behavior, a hallmark of a single functionally equivalent population of cells dividing at the same rate (Fig. 2C and fig. S6, A, B, and E) (18-21). Studies of interfollicular epidermis (IFE) revealed that this pattern of clonal evolution was consistent with progenitors dividing stochastically to generate differentiated and cycling daughters with equal probability (18, 19). By implementing a Bayesian inference analysis, we showed that the entire data set conforms to the IFE paradigm (Fig. 2E; fig. S6, C to E; and supplementary theory). We conclude that esophageal progenitors (EP) are functionally equivalent.. The observation of similar progenitor behavior in EE and epidermis, derived from endoderm and ectoderm, respectively, argues that squamous epithelia share a common mechanism of homeostasis irrespective of their developmental origin. However, EP behavior differs ...
Andersson E, Villabona L, Bergfeldt K, Carlson J, Ferrone S, Kiessling R, Seliger B, Masucci G. Correlation of HLA-A02* genotype and HLA class I antigen down-regulation with the prognosis of epithelial ovarian cancer. Cancer Immunol Immunother. 2012; 61:1243-53.. Buettner M, Xu H, Böhme R, Seliger B, Jacobi J, Wiesener M, Benz K, Amann K. Predominance of Th2 cells and plasma cells in polyoma virus nephropathy: a role for humoral immunity? Hum Pathol. 2012; 43:1453-62.. Lichtenfels R, Rappl G, Hombach A, Recktenwald C, Dressler S, Abken H, Seliger B. A proteomic view at T cell costimulation. PLoS One. 2012; 7:e32994.. Stölzel F, Hackmann K, Kuithan F, Mohr B, Thiede C, Röllig C, Platzbecker U, Schetelig J, Schaich M, Seliger B, Hartmann A, Baretton G, Zietz C, Ehninger G, Schrock E, Bornhäuser M. Clonal evolution including partial loss of MHC-I genes favoring extramedullary AML relapse after allogeneic HSCT. Transplantation. 2012; 93:744-9.. Okita R, Mougiakakos D, Ando T, Mao Y, Sarhan D, ...
Here are some very clear clips for the immune responses to infection, starting with a really well done explanation of Burnets Nobel-winning clonal selection theory: If you like that, check out some more of the videos from the Walter and Eliza Hall Institute of Medical Research. Try this animation and quiz: McGraw Hill Online Centre…
10 janvier Acquisition Adulte relais Contrat enfance jeunesse Décision modificative Électricité église Emploi Indemnité receveurs
Tasmanian devils have been considered livestock predators. In reality, these marsupials take most of their large prey, such as wombats, wallabies, sheep, and rabbits, in the form of carrion. Tasmanian devils are efficient scavengers, eating even bones and fur. Tasmanian devils may have depended on carrion left from Tasmanian wolf kills in historical times. Other food items, such as insects, insect larvae, snakes, and small amounts of vegetation, are taken when encountered. Tasmanian devils forage in a slow, lumbering manner, using their sense of smell to find food at night. They are famous for their rowdy communal feeding, which is accompanied by aggression and loud vocalisations ...
Tasmanian devils are breeding at younger ages, and researchers at the University of Tasmania in Australia believe the phenomenon is caused by an evolutionary response to the cancer that is devastating these small marsupials.. Devil facial tumor disease (DFTD) is a contagious form of cancer that has been infecting the animals since 1996.1 Tasmanian devils are carnivorous marsupials of the family Dasyuridae. These nocturnal predators are found exclusively on the island of Tasmania and are comprised of about 50 species. They have a normal life span of five to six years, usually breeding around the ages of two or three. However, since the disease is cutting their total years down to two or three, most females would ordinarily not live to rear their first litter.. Since the onset of the epidemic, Tasmanian devils have begun to breed as early as age one. We could be seeing evolution occurring before our eyes. Watch this space! zoologist Menna Jones of the university said in an interview with the ...
Personalize your 15in with the Tasmanian Devil Swirl Cream 15in Skin by Skinit. Buy the Tasmanian Devil Swirl Cream 15in Skin online now.
TY - GEN. T1 - Inferring intra-tumor heterogeneity from high-throughput DNA sequencing data. AU - Oesper, Layla. AU - Mahmoody, Ahmad. AU - Raphael, Benjamin J.. PY - 2013/4/3. Y1 - 2013/4/3. N2 - Cancer is a disease driven in part by somatic mutations that accumulate during the lifetime of an individual. The clonal theory [1] posits that the cancerous cells in a tumor are descended from a single founder cell and that descendants of this cell acquired multiple mutations beneficial for tumor growth through rounds of selection and clonal expansion. A tumor is thus a heterogeneous population of cells, with different subpopulations of cells containing both clonal mutations from the founder cell or early rounds of clonal expansion, and subclonal mutations that occurred after the most recent clonal expansion. Most cancer sequencing projects sequence a mixture of cells from a tumor sample including admixture by normal (non-cancerous) cells and different subpopulations of cancerous cells. In addition ...
A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. [Cell] Full Article , Press Release , Graphical Abstract Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Mediated by a Reversible Drug-Tolerant State Barcode-mediated clonal tracking and genomic sequencing of patient-derived xenograft tumors revealed that residual tumors remaining after treatment with standard frontline chemotherapies, doxorubicin combined with cyclophosphamide, maintained the subclonal architecture of untreated tumors, yet their transcriptomes, proteomes, and histologic features were distinct from those of untreated tumors. [Sci Transl Med] Abstract , Press Release PDGFRα+ Stromal Adipocyte Progenitors Transition into ...
Tasmanian Devils were so named for their crabby, aggressive behavior (especially around food and mating time) and the absolutely bizarre sounds that they make. They are solitary, non-monogamous, nocturnal animals, and live in burrows. Devils eat a wide variety of other creatures, though they typically only hunt things that are smaller than themselves. They also consume carrion, and thanks to their powerful teeth and jaws, are able to completely consume an animal. Devils are at their most aggressive when feeding, as it is a time that the normally solitary creatures come together and (attempt to) share a meal ...
Despite recent advances in the treatment of multiple myeloma, the disease constantly relapses and is still considered as incurable. The current knowledge about the biological mechanisms underlying resistance to the different class of drugs in multiple myeloma remains poor. The primary objective of the MYRACLE (Myeloma Resistance And Clonal Evolution) cohort, a multicenter prospective cohort of patients with multiple myeloma, is to address this limitation. We here describe the study background, design and methods used for this cohort. All patients (| 18 year old) diagnosed with de novo or relapsed multiple myeloma and treated in two hematology department from west of France are included in the MYRACLE cohort. Patients provide a signed informed to be included in the study. All subjects are followed until refusal to participate in the study or death. The MYRACLE cohort prospectively collects data on socio-economic status, medical status, imaging, prognosis factors, MM therapies and associated events
WES of patient-matched tumor pairs from 23 individuals with HNSCC demonstrates the intertumor genetic heterogeneity of this cancer. To our knowledge, this is the first study of HNSCC to examine intertumor genetic heterogeneity in synchronous nodal metastases and metachronous recurrence across multiple patients; it provides a model to determine patterns of mutation and clonal evolution that may be targetable for the treatment of recurrent/metastatic disease.. Primary tumors in our study averaged 67.6 nonsynonymous SSNVs per tumor, including mutations in tumor suppressor genes, oncogenes, and genes that have previously been found to be significantly mutated in HNSCC, such as AJUBA, CASP8, FAT1, FBXW7, NFE2L2, and TP53 (Supplemental Table 10 and Supplemental Table 4). Interestingly, primary tumors were not found to harbor mutations in several tumor suppressor genes and oncogenes previously implicated in HNSCC, including CCND1, PIK3CA, NOTCH1, PTEN, CDKN2A, HRAS, and EGFR. However, copy number ...
Malignant melanoma is a cancer form with particularly poor response to conventional chemotherapy, but where novel immunotherapies hold great promise. We have two ongoing projects focusing on this disease: In one project, we study the clonal evolution of metastatic spread in advanced melanoma patients and assess how different metastases within the same patients are. In a second project we analyse the genetic causes behind the disease in families were individuals have a very high risk of developing melanoma at an early age.. Key publications: Birkeland, E., Zhang, S., Poduval, D., Geisler, J., Nakken, S., Vodak, D., Meza-Zepeda, L.A., Hovig, E., Myklebost, O., Knappskog, S., Lønning P.E. (2018) Patterns of genomic evolution in advanced melanoma. Nature Communications. Provisionally accepted. ...
Australian scientists said on Thursday they had made a breakthrough in the fight to save the cancer-hit Tasmanian devil by mapping the species genome for the first time.
The Tasmanian devil, another iconic animal of Tasmania, is now the islands largest surviving carnivorous marsupial. It is known for its powerful jaws and scream-like vocalizations. Tasmanian devils are also unique because they suffer from devil facial tumor disease - an infectious, non-viral parasitic cancer which they can transmit to one another through fighting. While the unusual disease makes the animals of interest to cancer researchers, it is threatening the survival of the remaining Tasmanian devils, whose wild population has declined by 70 percent during the past 20 years ...
The former chief of Eli Lilly USA is picked to replace Tom Price, who stepped down in September amid a controversy over the abuse of taxpayer-funded travel.. 0 Comments. ...
At AGBT, researchers described applications for rapid pathogen ID; evaluating DNA, RNA, and gene expression in one assay; and understanding tumor heterogeneity.
Clonal evolution[edit]. Main article: Somatic evolution in cancer. Just like a population of animals undergoes evolution, an ... Clonal evolution[edit]. Main article: Somatic evolution in cancer. While genetic and epigenetic alterations in tumor suppressor ... the process of carcinogenesis is formally a process of Darwinian evolution, known as somatic or clonal evolution.[60] ... Nowell PC (October 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260): 23-8. Bibcode:1976Sci...194... ...
Loxdale HD, Lushai G. (2003) Rapid changes in clonal lines: the death of a 'sacred cow'. Biological Journal of the Linnean ... Loxdale HD (2009) What's in a clone: the rapid evolution of aphid asexual lineages in relation to geography, host plant ... Loxdale has written reviews on absence of strict genetic uniformity in populations of clonal organisms such as aphids. This ... These include the migration and dispersal of insects in relation to their genotype and habitat; intra-clonal genetic variation ...
Among the clonal population of these aphids, there may be several distinct morphs and this lays the foundation for a possible ... Chen, Rui; Wang, Zhe; Chen, Jing; Jiang, Li-Yun; Qiao, Ge-Xia (2017). "Insect-bacteria parallel evolution in multiple-co- ... However, there are differences between these sexual social insects and the clonal aphids, which are all descended from a single ... Eggs are parthenogenetically produced without meiosis and the offspring are clonal to their mother, so they are all female ( ...
... better known as the somatic evolution model. The clonal evolution model, which occurs in both the CSC model and stochastic ... According to the "stochastic model" (or "clonal evolution model") every cancer cell in a tumor could gain the ability to self- ... 4). These two models are not mutually exclusive, as CSCs themselves undergo clonal evolution. Thus, the secondary more dominant ... Nowell PC (October 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260): 23-8. Bibcode:1976Sci...194... ...
The clonal evolution model was first proposed in 1976 by Peter Nowell. In this model, tumours arise from a single mutated cell ... These are the cancer stem cell model and the clonal evolution model. The models are not mutually exclusive, and it is believed ... Stem cell variability is often caused by epigenetic changes, but can also result from clonal evolution of the CSC population ... This has been suggested as a reliable method for tracking clonal evolution. However, this technique proves challenging in ...
... termed clonal evolution, drives progression towards more invasive stages. Clonal evolution leads to intra-tumour heterogeneity ... Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (August 2006). "Clonal origin and evolution of a transmissible cancer". ... This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the ... Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal ...
Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (August 2006). "Clonal origin and evolution of a transmissible cancer". ... Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A (September 2009). "Origins and evolution of a transmissible cancer". Evolution ... The evolution of transmissible cancer is unlikely, because the cell clone must be adapted to survive a physical transmission of ... The evolution of transmissible cancer has occurred naturally in other animal species, but-similarly to human cancer ...
"Dynamic evolution of clonal epialleles revealed by methclone". Genome Biology. 15 (9): 472. doi:10.1186/s13059-014-0472-5. ISSN ...
Murgia, C; Pritchard JK; Kim SY; Fassati A; Weiss RA (2006-08-11). "Clonal Origin and Evolution of a Transmissible Cancer". ... CS1 maint: discouraged parameter (link) Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A (2009). "Origins and Evolution of a ... Belov, Katherine; Jones, Elizabeth; Cheng, Yuanyuan (September 2015). "The origin, dynamics, and molecular evolution of ... Transmissible Cancer". Evolution. 63 (9): 2340-2349. doi:10.1111/j.1558-5646.2009.00724.x. PMID 19453727. Strakova, Andrea; ...
Clonal origin and evolution of a transmissible cancer. Cell. 2006 Aug 11;126(3):477-87. Gomez-Raya L, Olsen HG, Lingaas F, ...
Given this insignificant level of clonal mixing, there is a low chance for barriers to the evolution and propagation of an ... the researchers were able to examine the degree of clonal mixing in the colony. Clonal mixing is defined as the "mixing" of ... So, the researchers concluded that the aphids do not adapt to short-term changes in the colony via a reduction of clonal mixing ... However, further studies on colonies where the level of clonal mixing is predicted to be high would enable researchers to gain ...
2005): The Evolution of Agriculture in Insects. Annual Review of Ecology and Systematics, 36: 563-569. Malloch, D., and M. ... All ambrosia fungi are probably asexual and clonal. https://trec.ifas.ufl.edu/RAB-LW-2/pdfs/AB-LW-2016/Paul%20Rugman-Jones%20-% ...
Evolution; International Journal of Organic Evolution. 46 (6): 1935-1944. doi:10.1111/j.1558-5646.1992.tb01179.x. ISSN 1558- ... Avise, John C. (2015-07-21). "Evolutionary perspectives on clonal reproduction in vertebrate animals". Proceedings of the ... Schlupp, Ingo (2005). "The Evolutionary Ecology of Gynogenesis". Annual Review of Ecology, Evolution, and Systematics. 36: 399- ... Evolution. 34 (5): 917. doi:10.2307/2407997. hdl:2027.42/137459. ISSN 0014-3820. JSTOR 2407997.. ...
"Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. 2 (3): 567-573. doi: ... "Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. 2 (3): 567-573. doi: ... Günter Vogt (2010). "Suitability of the clonal marbled crayfish for biogerontological research: A review and perspective, with ... Development Genes and Evolution. 216 (4): 169-184. doi:10.1007/s00427-005-0041-8. PMID 16389558. ...
January 2012). "Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing". Nature. 481 (7382): ... A big contribution to cancer death and failed cancer treatment is clonal evolution at the cytogenetic level, for example as ... 2010). "Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors". Genome Biology. 11 (8): R82. ... October 2009). "Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution". Nature. 461 (7265): ...
McGovern, Tamara N. (2002). "Sex-ratio bias and clonal reproduction in the brittle star Ophiactis savignyi". Evolution. 56 (3 ...
... termed clonal evolution, drives progression towards more invasive stages.[76] Clonal evolution leads to intra-tumour ... "Clonal origin and evolution of a transmissible cancer". Cell. 126 (3): 477-87. doi:10.1016/j.cell.2006.05.051. PMC 2593932. ... This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the ... Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal ...
Clonal origin and evolution of a transmissible cancer. Cell. 2006 Aug 11;126(3):477-87. ...
2012). "Clonal evolution in relapsed acute myeloid leukemia revealed by whole-genome sequencing". Nature. 481 (7382): 506-10. ...
However, this fast evolution might also be due to these sequences' inability to repair DNA damage via template-assisted repair ... April 2018). "Clonal polymorphism and high heterozygosity in the celibate genome of the Amazon molly". Nature Ecology & ... Evolution of sexual reproduction Genetic hitchhiking Hill-Robertson effect Muller HJ (1932). "Some genetic aspects of sex". ... original paper as cited by, e.g.: Smith JM, Szathmary E (1997). The major transitions in evolution. Oxford, New York, Tokyo: ...
... clonal evolution or a phenotypic mimic?". Hum. Pathol. 32 (10): 1102-8. doi:10.1053/hupa.2001.28252. PMID 11679945. Itakura E; ... will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically ...
"Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer". Cancer ... This explains the concept of tumour heterogeneity and the order of genetic events during tumor evolution. Many of the genes ... The genetic profiles of primary and metastatic lesions in breast carcinomas show a large extent of clonal pertinence between ... "Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution". Nature. 461 (7265): 809-13. doi: ...
"Journal of Evolution and Technology. 13.. [permanent dead link] *^ Cohen, Haley (31 July 2015). "How Champion-Pony Clones Have ... "Moving Toward a Clonal Man: Is This What We Want?" The Atlantic Monthly (1971). ... Lederberg Joshua (1966). "Experimental Genetics and Human Evolution". The American Naturalist. 100 (915): 519-531. doi:10.1086/ ...
"Complex spatial clonal structure in the macroalgae Fucus radicans with both sexual and asexual recruitment". Ecology and ... Evolution. 5 (19): 4233-4245. doi:10.1002/ece3.1629. ISSN 2045-7758. PMC 4667831. PMID 26664675. "BAMBI, Baltic Sea Marine ...
According to the Clonal Evolution model proposed by Peter Nowell, a mutated cancer cell can accumulate more mutations as it ... "Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer". Nature ... Inferring Clonal Architecture and Tracking the Spatial and Temporal Patterns of Tumor Evolution". PLOS Computational Biology. ... Understanding clonal dynamics improves understanding on how related cancers such as MDS, MPN and sAML compare in risk and give ...
Evolution in bacteria was previously viewed as a result of mutation or genetic drift. Today, genetic exchange, or gene transfer ... This clonal nature leads to random mutations that occur during DNA replication that potentially helps bacteria evolve. It was ... The importance of evolution in bacterial recombination is its adaptivity. For example, bacterial recombination has been shown ... Shapiro, B. Jesse (2016-03-24). "How clonal are bacteria over time?". bioRxiv: 036780. doi:10.1101/036780. Levin, Bruce R.; ...
Paradis E, Claude J, Strimmer K (January 2004). "APE: Analyses of Phylogenetics and Evolution in R language". Bioinformatics. ... "Reconstruction of clonal trees and tumor composition from multi-sample sequencing data". Bioinformatics. 31 (12): i62-70. doi: ... Molecular Biology and Evolution. 23 (2): 254-67. doi:10.1093/molbev/msj030. PMID 16221896. Jobb G, von Haeseler A, Strimmer K ( ... Molecular Biology and Evolution. 29 (8): 1969-1973. doi:10.1093/molbev/mss075. PMC 3408070. PMID 22367748. Jiang Y, Qiu Y, Minn ...
"Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. 2 (3): 567-573. doi: ... March 2015). "Convergent evolution of the genomes of marine mammals". Nature Genetics. 47 (3): 272-5. doi:10.1038/ng.3198. PMID ... November 2007). "Evolution of genes and genomes on the Drosophila phylogeny". Nature. 450 (7167): 203-18. Bibcode:2007Natur.450 ... Genomic basis for the convergent evolution of electric organs". Science. 344 (6191): 1522-5. doi:10.1126/science.1254432. PMID ...
"Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. doi:10.1038/s41559-018- ... Günter Vogt (2010). "Suitability of the clonal marbled crayfish for biogerontological research: A review and perspective, with ... Development Genes and Evolution. 216 (4): 169-184. doi:10.1007/s00427-005-0041-8.. ...
... decreases impaired proliferation in response to antigenic stimulation the accumulation and the clonal expansion of memory and ... and harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution ...
"USDA Pecan Breeding Program, National Clonal Germplasm Repository for Pecans and Hickories". Horticulture Dept. Retrieved 6 Dec ... "Evolution, Phylogeny, and Systematics of Juglandaceae" (PDF). Annals of the Missouri Botanical Garden. Missouri Botanical ...
... especially evolution; one of the best known contemporary popular writers on evolution.[175][176] ... He won the Nobel Prize in 1960 for predicting acquired immune tolerance and was best known for developing the theory of clonal ... "Man's evolution as a neotenous ape has put him in a similar position to the dog's. He becomes sexually mature and yet he still ... R. L. Wysong (1976). "5: Origin of Proteins". The Creation-evolution Controversy (implications, Methodology and Survey of ...
Os poucos estudos que se fixeron sobre a dispersión clonal atoparon que a maioría dos xenotipos teñen distribucións xeográficas ... and evolution through psbA non-coding region genotyping. PlosOne e29013 ... Utilizando marcadores microsatélite para identificar xenotipos multilocus, pode resolverse unha soa liña clonal de Symbiodinium ... clonal) de Symbiodinium. Nalgunhas colonias poden aparecer xenotipos adicionais, mais é raro atopar máis de dous ou tres. Cando ...
Janeway CA, Jr (1 November 2013). "Pillars article: approaching the asymptote? Evolution and revolution in immunology. Cold ...
Bartlett, J. Blake; Dredge, Keith; Dalgleish, Angus G. (1 April 2004). "Timeline: The evolution of thalidomide and its IMiD ... Lenalidomide and pomalidomide are about 100-1000 times more potent in stimulating T-cell clonal proliferation than thalidomide ... data suggests this co-stimulation leads to increased Th1 type cytokine release of IFN-γ and IL-2 that further stimulates clonal ...
... and disease evolution can all be elucidated through single cell sequencing.[5] Single cell sequencing was selected as the ... a population of the same species can appear to be genetically clonal, but single-cell sequencing of RNA or epigenetic ... "Distant metastasis occurs late during the genetic evolution of pancreatic cancer". Nature. 467 (7319): 1114-7. Bibcode ... "High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes" ...
Evolution[edit]. In evolution, anastomosis is a recombination of evolutionary lineage. Conventional accounts of evolutionary ... fusing to form a genetic singular clonal colony that can cover hectares called a genet or just microscopical areas.[9] ...
Clonal Anergy theory, proposed by Nossal, in which self-reactive T- or B-cells become inactivated in the normal individual and ... Dunne DW, Cooke A (2005). "A worm's eye view of the immune system: consequences for evolution of human autoimmune disease". ... Clonal Deletion theory, proposed by Burnet, according to which self-reactive lymphoid cells are destroyed during the ... Clonal Ignorance theory, according to which autoreactive T cells that are not represented in the thymus will mature and migrate ...
Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components. It is one of the ... In these cases, myelofibrosis occurs as a result of somatic evolution of the abnormal hematopoietic stem cell clone that caused ... Further thoughts on the nosology of the clonal myeloid disorders". Leukemia. 19 (7): 1139-41. doi:10.1038/sj.leu.2403804. PMID ...
Unity, diversity and evolution. Ed.: Barry S. C. Leadbeater and J. C. Green Taylor and Francis, London 2000, p. 3. ... "Are eukaryotic microorganisms clonal or sexual? A population genetics vantage". Proceedings of the National Academy of ... Dacks J, Roger AJ (June 1999). "The first sexual lineage and the relevance of facultative sex". Journal of Molecular Evolution ... Eukaryotes emerged in evolution more than 1.5 billion years ago.[44] The earliest eukaryotes were likely protists. Although ...
Another method for in vitro clonal amplification is bridge PCR, in which fragments are amplified upon primers attached to a ... "Introducing 'dark DNA' - the phenomenon that could change how we think about evolution".. ... A polymerase chain reaction (PCR) then coats each bead with clonal copies of the DNA molecule followed by immobilization for ... which involves the clonal amplification of DNA on a surface. The cluster technology was co-acquired with Lynx Therapeutics of ...
... spreads into large clonal colonies, which contribute to its being considered a noxious weed in some places.[1][3] ... "Phylogeny of Opuntia s.s. (Cactaceae): Clade delineation, geographic origins, and reticulate evolution". American Journal of ...
Barlow, Connie (2000). The Ghosts of Evolution: Nonsensical Fruit, Missing Partners, and Other Ecological Anachronisms. New ... Here it can form large clonal colonies, reproducing by shoots sprouting from roots. ...
Gillespie JH (November 2001). "Is the population size of a species relevant to its evolution?". Evolution; International ... "clonal") organisms). ... Natural selection and evolutionEdit. Main article: Evolution. ... In evolution, this chromosome has lost most of its content and also most of its genes, while the X chromosome is similar to the ... Staub JE (1994). Crossover: Concepts and Applications in Genetics, Evolution, and Breeding. University of Wisconsin Press. p. ...
Craven, Hamilton (1978) The Triumph of Evolution: The Heredity-Environment Controversy, 1900-1941: "While it would be ... The heritability index for all traits would be zero (all variability between clonal individuals must be due to environmental ... Darwin's Theory of Evolution steered naturalists such as George Williams and William Hamilton to the concept of personality ... Symons, D. (1979). The evolution of human sexuality. Oxford: Oxford University Press.. ...
Myriad receptors are produced through a process known as clonal selection.[1][2] According to the clonal selection theory, at ... EvolutionEdit. The acquired immune system, which has been best-studied in mammals, originated in jawed fish approximately 500 ... The evolution of the AIS, based on Ig, TCR, and MHC molecules, is thought to have arisen from two major evolutionary events: ... Rogozin IB, Iyer LM, Liang L, Glazko GV, Liston VG, Pavlov YI, Aravind L, Pancer Z (June 2007). "Evolution and diversification ...
Stavnezer J, Amemiya CT (2004). "Evolution of isotype switching". Semin. Immunol. 16 (4): 257-275. doi:10.1016/j.smim.2004.08. ... Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus ... This recombinational process that produces clonal antibody paratope diversity is called V(D)J or VJ recombination. Basically, ... "V(D)J recombination and the evolution of the adaptive immune system". PLoS Biol. 1 (1): E16. doi:10.1371/journal.pbio.0000016 ...
Clonal fragmentation[edit]. Main article: Fragmentation (reproduction). Fragmentation in multicellular or colonial organisms is ... Samson, RY; Bell, SD (November 2009). "Ancient ESCRTs and the evolution of binary fission". Trends in Microbiology. 17 (11): ... "Evolution of diverse cell division and vesicle formation systems in Archaea". Nature Reviews. Microbiology. 8 (10): 731-41. ...
David R. Harris, Gordon C. Hillman, Foraging and Farming: The Evolution of Plant Exploitation. Routledge, 2014 ISBN 1-317-59829 ... The consistent parenchyma tissue, the clonal nature of the plant and the low metabolic activity provide a very nice "model ... Hawkes, J.G. (1990). The Potato: Evolution, Biodiversity & Genetic Resources, Smithsonian Institution Press, Washington, DC ...
Stanley Michael Gartler used X chromosome inactivation to demonstrate the clonal origin of cancers. Examining normal tissues ... "Sex-differential selection and the evolution of X inactivation strategies". PLoS Genetics. 9 (4): e1003440. doi:10.1371/ ... "Evaluation of clonal origin of malignant mesothelioma". Journal of Translational Medicine. 12: 301. doi:10.1186/s12967-014- ...
Origin and evolution[edit]. Relationship of major animal lineages with indication of how long ago these animals shared a common ... see clonal colony). ... Studies on the evolution of the placenta have identified a ... Griffith, Oliver W.; Wagner, G?nter P. (23 March 2017). "The placenta as a model for understanding the origin and evolution of ... vertebrate organs". Nature Ecology & Evolution. 1 (4): 0072. doi:10.1038/s41559-017-0072.. ...
Katz Ezov et al.[43] presented evidence that in natural S. cerevisiae populations clonal reproduction and selfing (in the form ... McBryde C, Gardner JM, de Barros Lopes M, Jiranek V (2006). "Generation of novel wine yeast strains by adaptive evolution". ... In nature, mating of haploid cells to form diploid cells is most often between members of the same clonal population and out- ...
Evolution; international journal of organic evolution. 57 (6): 1255-1269. doi:10.1554/02-445.. ... The Great Banyan - a F. benghalensis, a clonal colony and once the largest organism known ... Evolution. Society for the Study of Evolution. 33 (2): 673-685. doi:10.2307/2407790. JSTOR 2407790.. ... recent genetic and molecular dating analyses have shown a very close correspondence in the character evolution and speciation ...
Clonal origin and evolution of a transmissible cancer»։ Cell 126 (3): 477-87։ August 2006։ PMC 2593932։ PMID 16901782։ doi: ...
"Redefining the structure of the hair follicle by 3D clonal analysis". Development. 139 (20): 3741-3751. doi:10.1242/dev.081091 ... Evolution of hair. ReferencesEdit. *^ Natural Hair Growth. Cardiff, United Kingdom: Health4sure. 2018.. .mw-parser-output cite. ...
EvolutionEdit. The evolution of fertilisation is related to the origin of meiosis, as both are part of sexual reproduction, ... "Simultaneous Mendelian and clonal genome transmission in a sexually reproducing, all-triploid vertebrate". Proceedings of the ... "The evolution of selfing in Arabidopsis thaliana". Science. 317 (5841): 1070-2. doi:10.1126/science.1143153. PMID 17656687.. ... Evolution. 57 (2): 216-30. doi:10.1111/j.0014-3820.2003.tb00257.x. PMID 12683519.. ...
Jans C, Meile L, Lacroix C, Stevens MJ (July 2015). "Genomics, evolution, and molecular epidemiology of the Streptococcus bovis ... of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion ... equinus complex (SBSEC)". Infection, Genetics and Evolution. 33: 419-36. doi:10.1016/j.meegid.2014.09.017. PMID 25233845.. ... also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution ...
2008). The Cyanobacteria: Molecular Biology, Genomics and Evolution (1st ed.). Caister Academic Press. ISBN 978-1-904455-15-8. ... While traditional microbiology and microbial genome sequencing rely upon cultivated clonal cultures, early environmental gene ... evolution, and mapping of genomes. Genomics aims at the collective characterization and quantification of genes, which direct ... DNA molecules and primers are first attached on a slide and amplified with polymerase so that local clonal colonies, initially ...
a) Branching clonal architecture of clonal evolution in cancer. Selective pressures allow some mutant sub-clones to expand ... Divergent (branching) clonal evolution of cancer with topographical separation.. In each example, a clonal (single cell) ... Clonal evolution in cancer.. Greaves M1, Maley CC.. Author information. 1. Division of Molecular Pathology, The Institute of ... Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive ...
The dynamics are complex, with highly variable patterns of genetic diversity and resulting clonal architecture. Therapeutic ... genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. ... Cancers evolve by a reiterative process of clonal expansion, ... Cancers evolve by a reiterative process of clonal expansion, ... Clonal evolution in cancer Nature. 2012 Jan 18;481(7381):306-13. doi: 10.1038/nature10762. ...
Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of ... Breast tumor heterogeneity: cancer stem cells or clonal evolution?. Campbell LL1, Polyak K. ... suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor ...
Landscape of somatic mutations and clonal evolution in mantle cell lymphoma Message Subject (Your Name) has sent you a message ... Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Sílvia Beà, Rafael Valdés-Mas, Alba Navarro, ... Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our ...
Researchers sequenced samples from hundreds of individuals with aplastic anemia to narrow in on somatic mutation and clonal ... Home » Tools & Technology » Sequencing » Sequencing Offers Clues to Clonal Evolution in Aplastic Anemia ... Sequencing Offers Clues to Clonal Evolution in Aplastic Anemia. Jul 02, 2015 ... researchers from the US and Japan described mutation and clonal dynamic patterns in aplastic anemia - a non-cancerous condition ...
It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patients cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.. ...
Molecular evolution of the Escherichia coli chromosome. III. Clonal frames. Message Subject (Your Name) has forwarded a page to ... Molecular evolution of the Escherichia coli chromosome. III. Clonal frames.. R Milkman and M M Bridges ... Molecular evolution of the Escherichia coli chromosome. III. Clonal frames.. R Milkman and M M Bridges ... Molecular evolution of the Escherichia coli chromosome. III. Clonal frames.. R Milkman and M M Bridges ...
This evidence, along with models of clonal interference (1-4), allows certain properties of the adaptive evolution of RNA ... suggests that clonal interference may play an important role in their adaptive evolution. Our goal here is to infer the ... The clonal interference model used to estimate μb andE(s) makes two important assumptions. The first is that selection ... The model of clonal interference (4) has the additional advantage of allowing us to estimate the beneficial mutation rate (μb) ...
... Leukemia. 2014 Jan;28(1):34-43. doi: 10.1038/leu. ... New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the ... They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the ...
Fishplot of clonal evolution and (D) clonal admixture of individual samples. (E) Clonal evolution tree with branch length ... 2 Clonal evolution in mCRC: From primary to metastasis and patient-derived xenograft.. Each patients clonal history is ... We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. ... Our clonal evolution models revealed four cases (CRC3, CRC8, CRC9, and CRC10) where the clonal marker variants of the ...
Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. Koichi ... Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia ... These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution ... supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. ...
Exome, Targeted Sequencing of Biopsy, ctDNA Reveals Clonal Evolution of Breast Cancer Tumors. Nov 16, 2015 ... Home » Exome, Targeted Sequencing of Biopsy, ctDNA Reveals Clonal Evolution of Breast Cancer Tumors ... tumor DNA to characterize the genomic architecture of a breast cancer patients tumor and track its clonal evolution over time ...
Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the ... Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. Ugo Testa * , Germana ... Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the ... Testa U, Castelli G, Pelosi E. Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem ...
Origins and clonal evolution of childhood leukaemia. Add to your list(s) Download to your calendar using vCal ... University of Cambridge , Talks.cam , Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer , Origins and clonal ... Overall, our studies suggest that clonal selection in leukaemia results from the combined influence of genetic and epigenetic ...
Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution. ...
Fifteen patients had clonal evolution alone (AP-CE), 32 had AP features but no evidence of clonal evolution (HEM-AP), and 24 ... and a third group had accelerated phase features plus clonal evolution (HEM-AP + CE, n = 24) (Table4). Clonal evolution ... The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Michael E. ODwyer, Michael ... The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood, 100(5), 1628-1633. ...
Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ...
Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex ( ... Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci Mingliang Chen1. , Odile B. ... Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci. ... Phylogenetic tree and data of clonal complex 4821 Neisseria meningitidis sublineage L44.1 (ChinaCC4821-R1-C/B) isolates. Red ...
Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex ( ... Guo Q, Mustapha MM, Chen M, Qu D, Zhang X, Chen M, et al. Evolution of sequence type 4821 clonal complex meningococcal strains ... Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci On This Page ... Evolution of sequence type 4821 clonal complex hyperinvasive and quinolone-resistant meningococci. Emerg Infect Dis. 2021 Apr [ ...
... Olsson, Linda LU ; Paulsson, ... Clonal Evolution through Loss of Chromosomes and Subsequent Polyploidization in Chondrosarcoma.}, url = {https://lup.lub.lu.se/ ...
Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Message Subject (Your Name) has sent you a message from ...
... and TP53 mutations during clonal evolution in CLL. We proceeded with a detailed review of all dominant clonal changes in paired ... Clonal Evolution, Genomic Drivers, and Effects of Therapy in Chronic Lymphocytic Leukemia. Peter Ouillette, Kamlai Saiya-Cork, ... Overall, clonal evolution and acquisition involving aCNAs was detected in 21 of these cases, novel cn-LOH developed in 6 cases ... Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, ...
Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia. Authors. MALČÍKOVÁ ... Using ultra-deep next-generation sequencing (NGS), we performed a detailed analysis of TP53 mutations clonal evolution. We ... Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia ...
Study Identifies Factors in Clonal Evolution of Chemotherapy-Resistant Urothelial Carcinoma. By Matthew Stenger. December 25, ... 1. Faltas BM, Prandi D, Tagawa ST, et al: Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet 48:1490- ... Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal ... Clonal Mutations. Chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion ...
Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ...
Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy Message Subject (Your Name) has forwarded a ...
To our knowledge, this is the first report of clonal evolution involving chromosome 5 occurring during the evolution of MDS ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ...
Evolution" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications ... Incidence of disease correlated with Daphnia clonal turnover*, ... The clonal make‐up and turnover of the Daphnia host population ... Clonal diversity, clonal persistence and rapid taxon replacement in natural populations of species and hybrids of the Daphnia ... Copyright © 2018, Society for the Study of Evolution. ISSN. 0014-3820. eISSN. 1558-5646. D.O.I.. 10.1111/evo.13413. Publisher ...
Purpose: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been ... CE, clonal evolution model; PE, parallel evolution model; SG, same-gene model. ... According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is ... Clonal and Parallel Evolution of Primary Lung Cancers and Their Metastases Revealed by Molecular Dissection of Cancer Cells. ...
2008 The ecology of altruism in a clonal insect. In Ecology of social evolution (eds Korb J., Heinze J.). Berlin, Germany: ... The impact of clonal mixing on the evolution of social behaviour in aphids. John Bryden, Vincent A. A. Jansen ... 2007 The evolution of dispersal in a Levins type metapopulation model. Evolution 61, 2386-2397. (doi:10.1111/j.1558-5646.2007. ... The impact of clonal mixing on the evolution of social behaviour in aphids ...
  • Accurate allele frequencies are important for measuring subclonal heterogeneity and clonal evolution. (biomedcentral.com)
  • Our method simplifies PCR duplicate identification and emphasizes their removal in studies of tumor heterogeneity and clonal evolution. (biomedcentral.com)
  • The challenge in precision medicine has been improving the understanding of cancer heterogeneity and clonal evolution, which has major implications in targeted therapy selection and disease monitoring. (missionbio.com)
  • Clonal interference also increases the time between fixations, thereby slowing the adaptation of asexual populations. (sciencemag.org)
  • Our goal here is to infer the presence of clonal interference acting on viral populations. (sciencemag.org)
  • Wolinska, Justyna 2018-01-01 00:00:00 According to the Red Queen hypothesis, clonal diversity in asexual populations could be maintained by negative frequency‐dependant selection by coevolving parasites. (deepdyve.com)
  • Significant differences in the clonal composition between random and infected subsamples of Daphnia populations were detected on six of seven tested occasions, confirming genetic specificity of the host-parasite interaction in this system. (deepdyve.com)
  • Assortment arises in structured populations and means that individuals interact with genetically similar individuals at a higher than average probability-promoting the evolution of social traits. (royalsocietypublishing.org)
  • Overall, our study provides a simple approach for removing PCR duplicates using an accessible deep-targeted sequencing kit and suggests that duplicates must be accounted for to obtain accurate frequency estimates important for studying heterogeneous populations, such as in studies of clonal evolution and cancer heterogeneity. (biomedcentral.com)
  • The fundamental hypothesis of our studies is that cancers consist of heterogeneous populations that can rapidly respond to stress (e.g. cytotoxic therapies) by exploiting fundamental principles of evolution. (asu.edu)
  • These behaviors are of major clinical significance for both primary and metastatic cancers where distinct clonal populations of tumor cells with variable evolutionary fitness are dispersed to multiple sites within a patient. (asu.edu)
  • Additionally, developing a method to place gene fusions in the context of (founder or sub-) clonal tumor cell populations will improve our understanding of their role in tumor progression and treatment response. (grantome.com)
  • In a similar vein, other studies using the HUMARA technology had found that hematologic malignancies are clonal diseases even when there is no apparent chromosomal abnormality, and that there are pre-leukemic clonal populations which precede acute myeloid leukemia (AML). (wikipedia.org)
  • The combination of these two ideas, that clonal hematopoiesis might be common in the elderly population and that AML evolves from pre-leukemic populations, led to the hypothesis that malignancy-associated mutations could also contribute to asymptomatic clonal hematopoiesis in healthy individuals. (wikipedia.org)
  • The heterogeneity found in cells of carcinogenic tumours implies competition between sub-populations of cells in the tumour, hence clonal interference. (wikipedia.org)
  • Nearly 40% of AA patients carry somatic mutations in the PIGA gene manifested as clonal populations of cells with the paroxysmal nocturnal hemoglobinuria phenotype, and 17% of AA patients have loss of HLA class I alleles. (ashpublications.org)
  • Here, genomics analyses of isolates from this rapidly expanding clonal population offered an opportunity to observe the molecular evolutionary changes often obscured in more diverse populations. (biomedcentral.com)
  • Population genetic data from 34 isolates from bamboo rats in India, Thailand and Vietnam, and 273 isolates from humans in China, India, Thailand, and Vietnam show that recombination is most likely to occur across spatially and genetically limited distances in natural populations resulting in highly clonal population structure yet sexually reproducing populations. (plos.org)
  • Fungal pathogen populations show patterns ranging from globally recombining to endemic and clonal. (plos.org)
  • In a study published online today in the New England Journal of Medicine , researchers from the US and Japan described mutation and clonal dynamic patterns in aplastic anemia - a non-cancerous condition involving an immune attack on blood system cells that sometimes progresses to myelodysplastic syndrome and/or acute myeloid leukemia (AML). (genomeweb.com)
  • Because the high level of clonal heterogeneity in CLL may be fueled by clonal diversity within earlier B cell lineage cells, we propose to characterize marrow B cell precursors of CLL patients through targeted deep sequencing of patient leukemia specific mutations and integrated analysis of mutation profiling with mRNA expression at the single cell level (Aim 2). (grantome.com)
  • We have now used clonal stem and progenitor cell assays to show that the impact of a given mutation is dependent on whether it is acquired in a wild-type or a single mutant cell, meaning that the consequences of each mutation are shaped by the effects of the preceding mutation. (ncri.org.uk)
  • This new model is not only biologically compelling but also of significant clinical importance as knowledge of mutation order could predict stage of disease or treatment response based on the evolution of the stem cell compartment. (ncri.org.uk)
  • Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as neutral drift in the stem cell population. (wikipedia.org)
  • As the name suggests, clonal interference occurs in an asexual lineage ("clone") with a beneficial mutation. (wikipedia.org)
  • This has to do with the fact that clonal interference also influences another part of the reproductive strategy of a population, namely mutation rate. (wikipedia.org)
  • The concept of an "actionable mutation" is considered within a model of clonal dominance and heterogeneous tumor cell dependencies. (aacrjournals.org)
  • Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. (nih.gov)
  • The dynamics are complex, with highly variable patterns of genetic diversity and resulting clonal architecture. (nih.gov)
  • Overall, our studies suggest that clonal selection in leukaemia results from the combined influence of genetic and epigenetic variations. (cam.ac.uk)
  • genetic relationships among isolates are defined by clonal complexes (CCs) identified by multilocus sequence typing (MLST), which are surrogates for lineages ( 2 ). (cdc.gov)
  • Progression of malignant tumors is largely due to clonal evolution of the primary tumor, clones acquiring different sets of molecular genetic lesions. (urotoday.com)
  • In this model, metastasis represents the end stage of evolution, and the presence of genetic alterations responsible for the metastatic ability of tumor cells is predicted. (aacrjournals.org)
  • One of the principal goals of large-scale genome sequencing of somatic tissues is to uncover genetic loci under positive selection, so-called 'driver' genes, that lead to clonal expansions. (elifesciences.org)
  • Conversely, recent studies have revealed that clonal evolution of premalignant B-cell precursors toward leukemia as a result of in vivo infection exposure takes place through acquisition of secondary genetic events no related to mutated hotspots for AID activity in both patient-derived B-ALL and mouse models mimicking the human genetic predisposition to B-ALL. (cicancer.org)
  • Based on these observations we examined here, in two genetic approaches, whether AID is required for clonal evolution of pre-malignant B-cells in the etiology of infection-associated B-ALL. (cicancer.org)
  • Surprisingly, however, latency, penetrance and genetic characteristics of B-ALL was not affected by genetic deletion of Aid in Pax5-haploinsufficient mice, suggesting that AID was dispensable for clonal evolution in this model. (cicancer.org)
  • During the evolution of MM, tumour clones may acquire further genetic abnormalities, e.g. to allow them to further expand or compete for stromal niches within the bone marrow, such that within an individual patient, multiple genetically distinct clones may be present. (wikilite.com)
  • Prerequisite for its evolution is heritable genetic variation. (uni-konstanz.de)
  • While many of the genetic and epigenetic abnormalities in neoplasms are probably neutral evolution , many have been shown to increase the proliferation of the mutant cells, or decrease their rate of death ( apoptosis ). (wikipedia.org)
  • Modern descriptions of biological evolution will typically elaborate on major contributing factors to evolution such as the formation of local micro-environments, mutational robustness, molecular degeneracy , and cryptic genetic variation. (wikipedia.org)
  • The effects of germline genetic context on the selective pressures driving somatic clonal evolution are explored. (cdc.gov)
  • Elucidation of the molecular and genetic pathways driving clonal evolution may inform surveillance and risk stratification, and may lead to the development of novel therapeutic strategies. (cdc.gov)
  • The clonal diversity, genetic diversity and structure of Heliconia angusta (Heliconiaceae) were assessed using AFLP-markers. (cambridge.org)
  • First, clonal interference causes some beneficial mutations to be outcompeted by more-fit mutations that occur in the same genetic background. (genetics.org)
  • As the HUMARA assay is based on the epigenetic state of cells, the underlying genetic determinants of the clonal expansion remained to be uncovered. (wikipedia.org)
  • On the other hand, genetic diversity in specific clones of Ph + B-ALL that drive clonal evolution has recently come to light. (wiley.com)
  • Clonal hematopoiesis can be detected in a patient's blood or bone marrow by identifying genetic changes (eg, mutations or chromosomal abnormalities) that have developed during an individual's lifetime in a process called clonal evolution. (ashpublications.org)
  • The way ants interact is fundamentally different from how solitary organisms interact, and with these findings we know a bit more about the genetic evolution that enabled ants to create structured societies. (rockefeller.edu)
  • However, genetic data have shown the AIDS-associated pathogen Penicillium marneffei to have extensive spatial genetic structure at local and regional scales, and although there has been some genetic evidence that a sexual cycle is possible, this haploid fungus is thought to be genetically, as well as morphologically, asexual in nature because of its highly clonal population structure. (plos.org)
  • The rate of recombinational replacement and the average size of the replacements are estimated in a set of closely related strains in which a clonal frame is dotted with occasional stretches of DNA belonging to other clones. (genetics.org)
  • If common clones are selected against and rare clones gain a concomitant advantage, we expect that clonal turnover should be faster during parasite epidemics than between them. (deepdyve.com)
  • Darwinian evolution and tiding clones in multiple myeloma. (wikilite.com)
  • The course of clonal evolution of 2 related clones in the blood of a patient with Waldenstrom macroglobulinemia (WM) indicates the functional importance for the expression of the B-cell receptor for the survival of these malignant cells. (elsevier.com)
  • Examination of clonal evolution in chronic lymphocytic leukemia. (cdc.gov)
  • Clonal evolution explains unpredictable leukemia disease course By Lynda Williams, Senior medwireNews Reporter Researchers have revealed the complicated clonal evolution of chronic lymphocytic leukemia , giving insight into the variation in disease training course and its own response to treatment. (parkerfirstbaptist.org)
  • By applying this analysis approach to 149 chronic lymphocytic leukemia (CLL) cases, we discovered earlier and later cancer drivers, uncovered patterns of clonal evolution in CLL and linked the presence of subclones harboring driver mutations with adverse clinical outcome. (grantome.com)
  • dN/dS was originally developed in the context of species evolution using the Wright-Fisher process, a classical population genetics model that assumes that evolution occurs over very long timescales, which permits new mutations to fix within lineages. (elifesciences.org)
  • Comparative analysis with 923 GBS genomes belonging to CC1, CC19, and CC23 revealed that the evolution of CC17 is distinct from that of other human-adapted lineages and recurrently targets functions related to nucleotide and amino acid metabolism, cell adhesion, regulation, and immune evasion. (asm.org)
  • Validated "hits" that target genes essential for the evolution, maintenance, or persistence of neoplastic cell lineages represent highly favorable candidates for improved therapeutic strategies. (asu.edu)
  • The phenomenon of clonal interference also occurs in cancer and pre-cancer cell lineages within a patient. (wikipedia.org)
  • A key focus is on the identification of clonal lineages of B-cells undergoing the process of somatic hypermutation in germinal centres and the maturation pathways by which these lineages develop over time. (hindawi.com)
  • Gene set enrichment analysis identified clonal enrichment of mutations in pathways involved in transmembrane transport of small molecules (odds ratio [OR] = 1.9), indicating a role for multidrug-resistance mutations in the progression of advanced chemotherapy-treated disease. (ascopost.com)
  • Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been proposed to date. (aacrjournals.org)
  • A generally accepted model for tumor progression is the "clonal evolution" model. (aacrjournals.org)
  • In cancer research two fundamentally different mechanisms explaining tumor progression currently split the positions: Clonal evolution versus cancer stem cells. (micronaut.ch)
  • Clonal evolution is a key feature of cancer progression and relapse. (grantome.com)
  • Clonal hematopoiesis of indeterminate potential, or CHIP, is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells. (wikipedia.org)
  • In contrast to other conditions linked to clonal hematopoiesis, such as myelodysplastic syndrome (MDS) or clonal hematopoiesis of indeterminate potential in the elderly, the top alterations in AA are closely related to its immune pathogenesis. (ashpublications.org)
  • Testa U, Castelli G, Pelosi E. Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. (mdpi.com)
  • Clonal diversity, the source of ITH, is the characteristics of all cancers and plays a critical role in cancer invasion, metastasis and development of resistance to targeted and non-targeted therapies[ 1-4 ]. (jcmtjournal.com)
  • Using genetically-engineered mouse models that closely recapitulate human lung and pancreatic cancers, we have shown that gene mutations are permissive, but insufficient, to drive clonal cancer evolution, consistent with the need for additional cellular adaptations. (yale.edu)
  • Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. (yale.edu)
  • A large retrospective analysis suggests that baseline TL associate with late events of hematologic relapse and clonal evolution in aplastic anemia patients treated initially with anti-thymocyte globulin-based therapy. (springer.com)
  • Acquired aplastic anemia (AA) is an immune-mediated bone marrow aplasia that is strongly associated with clonal hematopoiesis upon marrow recovery. (ashpublications.org)
  • Classic prognostic factors, i.e., categorized ZAP70 and CD38 expressions as well as mutations in IGVH and NOTCH1 genes did not influence the course of clonal evolution in the examined group of patients. (cdc.gov)
  • Advances in next-generation genome analysis technology, including single nucleotide polymorphism arrays (SNP-A), targeted next-generation sequencing (NGS), whole-exome sequencing (WES), and NGS-based HLA typing, have generated several waves of studies of clonal evolution in AA, uncovering the near-ubiquitous presence of clonal hematopoiesis in the recovering marrow of AA patients. (ashpublications.org)
  • In conclusion, in patients with clonal evolution as the sole criterion of disease acceleration, good responses to imatinib are still possible. (bloodjournal.org)
  • The patients with clonal evolution died earlier, before reaching remission, that can be connected with heavy initial state and high frequency of relapse. (cytgen.com)
  • Molecular evolution of the Escherichia coli chromosome. (genetics.org)
  • In chronic myelogenous leukemia (CML), the development of chromosomal abnormalities in addition to the Philadelphia chromosome (clonal evolution) is considered by many to be a feature of accelerated phase (AP). (bloodjournal.org)
  • Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by a specific chromosomal translocation, t(9;22), resulting in a shortened chromosome 22, commonly referred to as the Philadelphia (Ph) chromosome. (bloodjournal.org)
  • 3 We report a patient with the 5q- syndrome , who had resistance to lenalidomide treatment, associated to emergence of clonal evolution involving chromosome. (haematologica.org)
  • According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is present on chromosome 11p. (aacrjournals.org)
  • In this thesis, the clonal evolution of deletions on chromosome 20q (del20q) and TET2, a member of the Ten-Eleven-Translocation (TET) family of genes, were studied. (unibas.ch)
  • Clonal chromosome aberrations belong to the most important prognostic and predictive factors in CLL. (cdc.gov)
  • Identity of abnormal chromosome structure at diagnosis and relapse of disease can be an evidence of the influence of chemical agent on establishment of some types of evolution of chromosome abnormalities in leukemic cells in AML in children. (cytgen.com)
  • During the Chilean epidemic, the pandemic strain consisted of a highly clonal population [ 8 ], which reproduced extensively in the Chilean shore lines, and shared its habitat with many other related species. (biomedcentral.com)
  • Genomic instability appears to cooperate with Darwinian selection to promote cancer formation through a process in which genomic aberrations occur at accelerated rates, and those alterations that provide a selective growth advantage lead to clonal evolution and expansion. (asu.edu)
  • 1 Although AA has long been noted for its association with clonal blood disorders paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndrome (MDS), the nearly ubiquitous presence of clonal hematopoiesis in AA was appreciated only recently, made possible by advances in cytogenetic and sequencing technologies ( Figure 1 ). (ashpublications.org)
  • 2:53 Skip to 2 minutes and 53 seconds This malignant phenotype is supported by the inherent features of stem cells - self renewal, and clonal expansion. (futurelearn.com)
  • This phenomenon, known as clonal interference, ensures that those beneficial mutations that do achieve fixation are of large effect. (sciencemag.org)
  • Gerrish and Lenski ( 4 ) modeled the fate of beneficial mutations by considering clonal interference among them as a major factor. (sciencemag.org)
  • He reasoned that the loss of beneficial mutations because of clonal interference inhibits the adaptivity of asexually reproducing species. (wikipedia.org)
  • 2 Clonal hematopoiesis is defined by a disproportionately large fraction of hematopoietic cells arising from a single stem cell or a multipotent hematopoietic progenitor. (ashpublications.org)
  • Of the various clonal complexes (CCs), CC17 is overrepresented in GBS-infected newborns for reasons that are still largely unknown. (asm.org)
  • Identification of clonal complexes. (asm.org)
  • BURST analysis was used to assign clonal complexes within the Oxford isolate collection. (asm.org)
  • For the major clonal complexes, the predicted clonal ancestors are shown in the central ring, SLVs are shown in the middle (solid) ring, and double-locus variants are shown in the outer (dashed) ring. (asm.org)
  • Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow. (asm.org)
  • Phylogenetic tree and data of clonal complex 4821 Neisseria meningitidis sublineage L44.1 (China CC4821-R1-C/B ) isolates. (cdc.gov)
  • Phylogenetic tree and data of clonal complex 4821 Neisseria meningitidis sublineage L44.3 isolates. (cdc.gov)
  • Expansion of quinolone-resistant Neisseria meningitidis clone China CC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. (cdc.gov)
  • In China, the national dissemination of hyperinvasive sequence type (ST) 4821 clonal complex (CC4821) meningococci led to a shift in IMD epidemiology from mostly MenA to predominantly MenC ( 3 , 4 ). (cdc.gov)
  • NEW YORK (GenomeWeb) - A public-private team from the US and UK has successfully used exome and targeted amplicon sequencing of tissue biopsies and circulating tumor DNA to characterize the genomic architecture of a breast cancer patient's tumor and track its clonal evolution over time in response to various therapies. (genomeweb.com)
  • Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations. (aacrjournals.org)
  • Interestingly, although the frequency of acquisition of changes in treated as opposed to untreated CLL was approximately 4-fold higher, the spectrum of genomic and mutational changes was largely similar, suggesting that the above cited and other recurrent genomic aberrations facilitate clonal dominance independent of, but aided by, therapies, and further that their origin is largely therapy independent. (aacrjournals.org)
  • Collectively, these results provide insights into clonal evolution underlying ibrutinib relapse and prompt further investigation on genomic abnormalities that have clinical application potential. (bloodadvances.org)
  • Clonal evolution and selection of tumor cells can be assessed by examining genomic and proteomic alterations of tumor samples obtained from multiple sites of primary and metastatic sites. (clinicaltrials.gov)
  • Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. (nih.gov)
  • Analysis of the research backing each concept, along with a review of the results of our recent study investigating putative breast cancer stem cells, suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor heterogeneity. (nih.gov)
  • Overall, parasitism seems to be a strong driver of host clonal turnover, in support of the Red Queen hypothesis. (deepdyve.com)
  • Appearance of unbalanced genome in evolution possess an advantage in proliferate activity and can be connected with the answer on chemotherapy. (cytgen.com)
  • This can be exemplified by pioneering studies at The Genome Institute leveraging deep, targeted sequencing of single nucleotide variants (SNVs) discovered using whole genome sequencing (WGS) to calculate variant allele frequencies (VAFs) for studying clonal evolution over time. (grantome.com)
  • The result, severe deficiencies in the ants' social behaviors and their ability to survive within a colony, both sheds light on a key facet of social evolution and demonstrates the feasibility and utility of genome editing in ants. (rockefeller.edu)
  • Almost 40 years ago, Peter Nowell suggested the clonal evolution cancer model. (futurelearn.com)
  • In 1976, Peter Nowell proposed the clonal evolution model of cancer and applied evolutionary models to understand tumor growth and treatment failure and the phenomenon of increased tumor aggressiveness that occurs during the natural history of advanced solid tumors ( 3 ). (aacrjournals.org)
  • New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the development of novel prognostic and therapeutic strategies. (nih.gov)
  • For all these reasons it is worthy to explore the evolution over time of antibiotic nonsusceptibility and its relation to clonality, since it may have preventive and therapeutic consequences. (asm.org)
  • Genes associated with pathways disrupted by selected clonal aberrations in neoplastic genomes in vivo can then be functionally interrogated in RNAi-based assays to evaluate their potential as therapeutic targets. (asu.edu)
  • I will discuss some of our recent findings in PDA genomes and the role of clonal behaviors in mediating therapeutic responses. (asu.edu)
  • Thus, the integrin-binding domain of CD98 is required for Ag-driven T cell clonal expansion in the pathogenesis of an autoimmune disease and may represent a useful therapeutic target. (jimmunol.org)
  • Exposures, the constitutive genetics of the host cells, systemic regulators, local regulators and architectural constraints all impinge upon and constrain the evolution of somatic cells. (nih.gov)
  • Somatic evolution is the accumulation of mutations and epimutations in somatic cells (the cells of a body, as opposed to germplasm and stem cells ) during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. (wikipedia.org)
  • Breast tumor heterogeneity: cancer stem cells or clonal evolution? (nih.gov)
  • We have recently demonstrated in human malignancies that the evolution of a tumour is also influenced by the order in which its mutations are acquired. (ncri.org.uk)
  • The earliest ideas about neoplastic evolution come from Boveri [8] who proposed that tumors originated in chromosomal abnormalities passed on to daughter cells. (wikipedia.org)
  • In the decades that followed, cancer was recognized as having a clonal origin associated with chromosomal aberrations. (wikipedia.org)
  • This research was aimed at observing clonal evolution in CLL at the chromosomal level, and assessing its clinical significance in relation to selected prognostic factors. (cdc.gov)
  • Andreieva S.V., Drozdova V.D., Kavardakova N.V. Phenomenon of the evolution of clonal chromosomal abnormalities in childhood acute myeloid leukemia, Tsitol Genet. (cytgen.com)
  • Clonal interference does not only play a role in the fixation of mutations in chromosomal DNA, but it also influences the stability or persistence of extrachromosomal DNA in the form of plasmids. (wikipedia.org)
  • Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the occurrence of a temporal tumor heterogeneity. (mdpi.com)
  • One is "the parallel evolution model," which proposes early occurrence of metastasis and parallel evolution of primary and metastatic tumors ( 13 ). (aacrjournals.org)
  • The parallel evolution model has been very applicable to the metastatic pattern of several solid epithelial tumors ( 15 - 17 ). (aacrjournals.org)
  • Currently, NGS has provided a high-resolution snapshot of the oligoclonal composition and evolution within tumors. (grantome.com)
  • from Niigata University, Japan, has published the article entitled "Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium " in Cell Reports . (endonews.com)
  • Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. (asm.org)
  • Two popular concepts, the clonal evolution model and the cancer stem cell model, attempt to answer how cancer propagates. (futurelearn.com)
  • They represent clonal stem cell disorders with an inherent tendency towards leukemic transformation. (unibas.ch)
  • To investigate cytogenetic evolution after upfront autologous stem cell transplantation for newly diagnosed myeloma we retrospectively analyzed fluorescence in situ hybridization results of 128 patients with paired bone marrow samples from the time of primary diagnosis and at relapse. (haematologica.org)
  • Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. (ascopost.com)
  • Long-term prospective studies are needed to determine the true prognostic implications of clonal hematopoiesis in AA. (ashpublications.org)
  • In this review, the implications of "trunk and branch" tumor evolution for drug discovery approaches and emerging evidence that low-frequency somatic events may drive tumor growth through paracrine signaling fostering a tumor ecologic niche are discussed. (aacrjournals.org)
  • When this distribution falls off slower than exponentially, clonal interference alone reasonably describes which mutations dominate the adaptation, although it gives a misleading picture of the evolutionary dynamics. (genetics.org)
  • In this way, clonal interference influences the evolutionary dynamics of plasmid-host adaptation, resulting in faster stabilisation of plasmids in a population. (wikipedia.org)
  • This study provides the theoretical link between dN/dS values and selective coefficients in somatic evolution, and measures the DFE of mutations in human tissues. (elifesciences.org)
  • Transforming dN/dS values to selective coefficients in somatic evolution is an unaddressed problem. (elifesciences.org)
  • Ex vivo experimental studies have suggested that the expression of AID in precursor B cells may promote clonal evolution towards leukemia. (cicancer.org)
  • In patients who had Richter transformation, we found that the transformed cells were clonal descendants of circulating leukemia cells but continued to undergo evolution and drifts. (bloodadvances.org)
  • Clonal evolution explains unpredictable leukemia disease course By Lynda Williams. (parkerfirstbaptist.org)
  • Examination of the pathophysiology of these diseases has provided interesting insights into not only the hierarchy of leukemia stem cells but also their clonal evolution. (wiley.com)
  • The consequent accumulation of new mutations promotes the adaptability of the leukemia, contributing to clonal selection. (oncotarget.com)
  • however this method is broadly limited to somatic evolution in the blood ( Gibson and Steensma, 2018 ) (where it is feasible to take samples from healthy individuals over time) and in rare cases of patients under active surveillance. (elifesciences.org)
  • This article provides a brief, but comprehensive, review of our current understanding of clonal evolution in AA and concludes with 3 cases that illustrate a practical approach for integrating results of next-generation molecular studies into the clinical care of AA patients in 2018. (ashpublications.org)
  • Our patient showed no erythroid response to lenalidomide and clonal cytogenetic evolution that was unusual in the 5q- syndrome . (haematologica.org)
  • The relationship between the clonal hierarchy and phenotype disease over time are discussed. (biomedcentral.com)
  • New isolates of V. parahaemolyticus that are able to cause diarrhea in humans by ingestion of seafood periodically emerge through their continuous evolution in the ocean. (biomedcentral.com)
  • Changes in clonal dominance may be reflected by changes in monoclonal immunoglobulin production. (wikilite.com)
  • This, together with their potentially large effective population sizes and the fact that their reproduction is not obligately sexual, suggests that clonal interference may play an important role in their adaptive evolution. (sciencemag.org)
  • Clonal interference is a phenomenon in evolutionary biology, related to the population genetics of organisms with significant linkage disequilibrium, especially asexually reproducing organisms. (wikipedia.org)
  • The idea of clonal interference was introduced by American geneticist Hermann Joseph Muller in 1932. (wikipedia.org)
  • When Muller introduced the phenomenon of clonal interference, he used it to explain why sexual reproduction evolved. (wikipedia.org)
  • As clonal evolution could allow Bcr-Abl independent proliferation, we analyzed its impact on the outcome of 71 AP patients treated with 600 mg of imatinib mesylate. (bloodjournal.org)
  • The integrin-binding domain of CD98 was necessary and sufficient for full clonal expansion, pointing to a role for adhesive signaling in T cell proliferation and autoimmune disease. (jimmunol.org)
  • Chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways. (ascopost.com)
  • Branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma. (ascopost.com)
  • Forest fragments commonly exhibit suboptimal site conditions, which can result in enhanced clonal reproduction, and a potential reduction in clonal diversity due to increased selfing and inbreeding depression. (cambridge.org)
  • Clonal diversity (Pd) of patches was slightly, yet significantly, lower in forest fragments compared with continuous forest. (cambridge.org)
  • The establishment of a clonal population may occur when a stem or progenitor cell acquires one or more somatic mutations that give it a competitive advantage in hematopoiesis over the stem/progenitor cells without these mutations. (wikipedia.org)
  • Divergent (branching) clonal evolution of cancer with topographical separation. (nih.gov)
  • Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? (biologists.org)
  • This allows evolution to proceed more rapidly, a phenomenon known as the Hill-Robertson effect. (wikipedia.org)
  • Finally, to define if subclonal mutations are predictive of clinical outcome, we will systematically identify clonal and subclonal mutations in serial samples prospectively collected from 300 subjects enrolled on a landmark phase III clinical trial of frontline fludarabine-based chemotherapy and characterize the dynamic changes in the clonal landscape within individual cases. (grantome.com)
  • Specifically, clinical presentation, risk of thrombosis, and clonal evolution are distinct in patients with myeloproliferative neoplasms who acquire JAK2V617F mutations prior to TET2 mutations compared to those that acquire TET2 mutations before JAK2V617F. (ncri.org.uk)
  • The objectives of this study were to determine the prevalence of clonal P. aeruginosa infection in Canada and to associate P. aeruginosa genotypes with clinical outcomes. (utoronto.ca)
  • Next-generation sequencing and cytogenetics studies of clonal hematopoiesis in acquired AA. (ashpublications.org)
  • The ability to predict hematologic response, relapse and clonal evolution could improve treatment allocation. (springer.com)
  • The important outcomes to be considered following IST are hematologic response, relapse and clonal evolution to MDS and survival. (springer.com)
  • Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases. (wikipedia.org)
  • This view gained mechanistic support in 2012 when it was found a number of the women who showed evidence for clonal hematopoiesis through X-inactivation skew also had mutations in the hematologic-malignancy-associated gene TET2. (wikipedia.org)
  • We can divide multicellularity into two distinct types, aggregative and clonal - which we will discuss in turn (1). (plos.org)