TY - JOUR. T1 - Loss of Pol32 in Drosophila melanogaster causes chromosome instability and suppresses variegation. AU - Tritto, Patrizia. AU - Palumbo, Valeria. AU - Micale, Lucia. AU - Marzulli, Marco. AU - Bozzetti, Maria Pia. AU - Specchia, Valeria. AU - Palumbo, Gioacchino. AU - Pimpinelli, Sergio. AU - Berloco, Maria. PY - 2015/3/31. Y1 - 2015/3/31. N2 - Pol32 is an accessory subunit of the replicative DNA Polymerase δ and of the translesion Polymerase ζ. Pol32 is involved in DNA replication, recombination and repair. Pol32 s participation in high- and low-fidelity processes, together with the phenotypes arising from its disruption, imply multiple roles for this subunit within eukaryotic cells, not all of which have been fully elucidated. Using pol32 null mutants and two partial loss-of-function alleles pol32rd1 and pol32rds in Drosophila melanogaster, we show that Pol32 plays an essential role in promoting genome stability. Pol32 is essential to ensure DNA replication in early ...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 ...
Pericentromeric demethylation and chromosomal instability induced by chemicals. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013 ...
Chromosome instability (CIN) is an inherent enabling characteristic of cancer important for tumor initiation and progression and is observed in a majority of tumors (1⇓-3). It has been proposed that alterations resulting in genome instability happen early during tumor formation, allowing the accumulation of errors during DNA replication, repair, and chromosome segregation, thereby increasing the likelihood that a cell will acquire multiple genetic changes necessary for tumor progression (4). CIN is possibly the major contributor to intratumoral heterogeneity-that is, the presence of genetically distinct populations of cells within a single tumor that impacts treatment strategy, drug resistance, and tumor evolution (5⇓⇓-8). For these reasons, defining genes and pathways that drive CIN and understanding the mechanisms that underlie genome stability will contribute not only to an understanding of tumor etiology and progression but will also be relevant for guiding therapeutic strategies. The ...
Birkness JE, Spada NG, Miller C, Luketich JD, Nason KS, Sun W, Davison JM. Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study. Genes Chromosomes Cancer. 2018 01; 57(1):28-34 ...
Principal Investigator:YAMASHITA Takayuki, Project Period (FY):1999 - 2000, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Hematology
Centrosomes play critical roles in processes that ensure proper segregation of chromosomes and maintain the genetic stability of human cells. They contribute to mitotic spindle organization and regulate aspects of cytokinesis and cell cycle progression. We and others have shown that centrosomes are abnormal in most aggressive carcinomas. Moreover, centrosome defects have been implicated in chromosome instability and loss of cell cycle control in invasive carcinoma. Others have suggested that centrosome defects only occur late in tumorigenesis and may not contribute to early steps of tumor development. To address this issue, we examined pre-invasive human carcinoma in situ lesions for centrosome defects and chromosome instability. We found that a significant fraction of precursor lesions to some of the most common human cancers had centrosome defects, including in situ carcinomas of the uterine cervix, prostate, and female breast. Moreover, centrosome defects occurred together with mitotic spindle
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been
Chromosomal loss and rearrangement are known to be important signs of genetic instability in cancer cells, but the mechanisms behind these changes are unclear. We have begun an investigation of the contribution of segregational errors to chromosomal instability using oral carcinoma cells as our model system. In these cultures, we found frequent variations in chromosome numbers and structure between different cells from the same tumor cell culture. We believe that many of these abnormalities can be explained by chromosomal segregational defects.. The OSCC cells clearly had difficulty achieving normal metaphase alignment and anaphase chromosome separation. One simple model is that the kinetochores are defective for movement, and that this single defect causes chromosomes to lag at both metaphase and anaphase. Consistent with this model, approximately equal numbers of lagging chromosomes were observed in both metaphase and anaphase cells. One way to test this directly would be a real-time analysis ...
Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have
MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Hannes Alfvén. Plasma instabilities are not well-known to the general public, or among astronomers. They refer to distortions that occur when plasmas are generated and confined. They are often confused with phenomena observed in fluid interactions: Kelvin-Helmholtz instabilities, or Rayleigh-Taylor instabilities, for instance.. Since plasmas are conventional matter with a small percentage of ionized particles, they do not conform to kinetic energy principles, alone. Rather, matter in the plasma state is strongly influenced by electromagnetism, and does not obey any other force, including gravity, except peripherally. Many types of instability are observed in plasma: diocotron instabilities, kink instabilities, edge instabilities (that make fusion reactors impossible to control), sausage instabilities (deformations in plasma flow), reactive instabilities, etc.. A principle tenet of Electric Universe theory is that various plasmas (mostly hydrogen ions and helium nuclei) comprise 99.99% of the ...
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Read "Chromosome instability and contents of heavy metals in amphibian from the Yugansk Reserve, Russian Journal of Ecology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Centrosome abnormalities and amplification are common characteristics of tumour cells. Aneuploidy and chromosomal instability are highly correlated with the appearance of multiple centrosomes.. ...
Principal Investigator:TAKUBO Kaiyo, Project Period (FY):2009 - 2011, Research Category:Grant-in-Aid for Scientific Research (B), Section:一般, Research Field:Human pathology
We and others have demonstrated that TIF1γ was a tumor suppressor (24, 27-29), whose mechanism of action has remained elusive. In this study, we demonstrated that stable Tif1γ inactivation resulted in SAC and postmitotic checkpoint attenuation, leading to the accumulation of severe chromosomal abnormalities. As a result, Tif1γ-inactivated cells present mitotic defects increasing their tumor aggressiveness in animal models. Finally, we observed that low TIF1γ expression was associated with increased CIN in different types of human tumors. Therefore, this work highlights an original mechanism by which TIF1γ behaves as a tumor suppressor through its role in the control of mitosis, whose impairment may represent a major tumor-suppressive process.. First of all, we revealed here that the immediate consequence of TIF1γ depletion in different cell types (primary and immortalized MEFs, transformed or immortalized epithelial cells) resulted in a proliferation arrest, mitotic blockade, accumulation ...
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.
Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce …
The epigenetic framework guides events like replication, repair and transcription, which in turn themselves leave an imprint on chromatin and chromosomal structure. Understanding how modulation of chromatin during replication and repair influence cell fate decisions in normal development and disease represents a major challenge. By bringing together leading scientists in chromatin, replication, repair and epigenetics, this conference aims to inspire discussions and new ideas on the interplay between chromosome architecture, epigenetic inheritance and genome duplication ...
An experiment is performed to assess the prevalence of instability in univariate and bivariate macroeconomic time series relations and to ascertain whether various adaptive forecasting techniques successfully handle any such instability. Formal tests for instability and out-of-sample forecasts from sixteen different models are computed using a sample of 76 representative U.S. monthly postwar macroeconomic time series, constituting 5700 bivariate forecasting relations. The tests indicate widespread instability in univariate and bivariate autoregressive models. However, adaptive forecasting models, in particular time varying parameter models, have limited success in exploiting this instability to improve upon fixed-parameter or recursive autoregressive forecasts. ...
BACKGROUND: Telomeres are repetitive DNA sequences and associated proteins that cap the ends of chromosomes. Functional telomeres protect genetic information and maintain chromosomal stability. Critically short telomeres ...
BACKGROUND: Telomeres are repetitive DNA sequences and associated proteins that cap the ends of chromosomes. Functional telomeres protect genetic information and maintain chromosomal stability. Critically short telomeres ...
Author: Perry Nickelston. Title: Five Hidden Signs of Instability. Summary: If you work with patients long enough, you come to realize a few in-the-trenches facts. Here are five biggies that require constant consideration...
Trouvez tous les livres de Schmeidler, Lacey - Instability, Liquidity and World Money. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783845404103
Haploids are a valuable tool for genomic studies in higher plants, especially those with huge genome size and long juvenile periods, such as conifers. In these species, megagametophyte cultures have been widely used to obtain haploid callus and somatic embryogenic lines. One of the main problems associated with tissue culture is the potential genetic instability of the regenerants. Because of this, chromosomal stability of the callus and/or somatic embryos should also be assessed. To this end, chromosome counting, flow cytometry and genotyping using microsatellites have been reported. Here, we present an overview of the work done in conifers, with special emphasis on the production of a haploid cell line in maritime pine (Pinus pinaster L.) and the use of a set of molecular markers, which includes Single Nucleotide Polymorphisms (SNPs) and microsatellites or Single Sequence Repeats (SSRs), to validate chromosomal integrity confirming the presence of all chromosomic arms.
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells?. ...
Chromosomal instability has long been recognized as a hallmark of cancer. Cancer progresses as cells override the intrinsic system of checks and balances that normally prevents them from dividing in the presence of a damaged or aneuploid genome. Chromosomal instability is described as increased chromosome missegregation and often results in aneuploidy or the condition of having too many or too few chromosomes. Under normal physiologic conditions, cell-cycle traverse is carefully controlled by sequential posttranslational modifications, especially E3 ligase-mediated ubiquitination (1, 2). The anaphase-promoting complex/cyclosome (APC/C) is a major E3 ligase complex that promotes the metaphase-to-anaphase transition, and its activation is inhibited until surveillance mechanisms within the cell sense proper metaphase alignment and bipolar spindle attachment of chromosomes (2, 3). Activation of the APC/C occurs via interaction with a cofactor that confers specificity to the complex, either FZR1/CDH1 ...
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells? close ...
In a new study, Dana-Farber Cancer Institute scientists disprove a century-old theory about why cancer cells often have too many or too few chromosomes, and show that the actual reason may hold the key to a novel approach to cancer therapy.. Since the late 19th century, scientists have attributed the surplus or shortage of intact chromosomes in cancer cells to a kind of fragmentation in cell division: instead of dividing neatly into two identical daughter cells, as normal cells do, cancer cells were thought to frequently split into three or four cells, each with a motley assortment of chromosomes. This explosive division was thought to occur because many cancer cells have extra centrosomes, tiny circular structures that help pairs of chromosomes line up in preparation for cell division.. When study lead author Neil Ganem, PhD, of Dana-Farber used newly developed microscope equipment to watch living cancer cells for a week or more, he found that not only were such abnormal divisions quite rare, ...
DNA ISH can be used to determine the structure of chromosomes. Fluorescent DNA ISH (FISH) can, for example, be used in medical diagnostics to assess chromosomal integrity. RNA ISH (hybridization histochemistry) is used to measure and localize mRNAs and other transcripts within tissue sections or whole mounts. ...
Ren, Y.; Lv, Q.; Yue, W.; Liu, B.; Zou, Z., 2019: The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
UniSA researchers at the Centre for Cancer Biology (CCB) have discovered a new aspect of cancer biology that may help to battle the spread and growth of tumours.. The research focuses on aneuploid cells, which are often associated with abnormal chromosome content and cell division - and how an enzyme known as caspase-2, initially discovered by the lead researcher 25 years ago, can act to prevent their growth.. Research leaders, Professor Sharad Kumar and Dr Loretta Dorstyn with PhD student Swati Dawar, have discovered that caspase-2, which is found in all mammals, has the capacity to suppress cancer growth by working to destroy aneuploid cells.. "Aneuploidy is a term that describes the abnormal chromosome content of a cell and occurs when there are failings during the normal division of a cell," Prof Kumar says.. "Aneuploidy is a feature of the majority of human tumours and is known to lead to chromosomal instability that can promote cancer onset and progression and cause drug ...
Structures of thin films bonded on thick substrates are abundant in biological systems and engineering applications. Mismatch strains due to expansion of the films or shrinkage of the substrates can induce various modes of surface instabilities such as wrinkling, creasing, period doubling, folding, ridging, and delamination. In many cases, the film-substrate structures are not flat but curved. While it is known that the surface instabilities can be controlled by film-substrate mechanical properties, adhesion and mismatch strain, effects of the structures curvature on multiple modes of instabilities have not been well understood. In this paper, we provide a systematic study on the formation of multimodal surface instabilities on film-substrate tubular structures with different curvatures through combined theoretical analysis and numerical simulation. We first introduce a method to quantitatively categorize various instability patterns by analyzing their wave frequencies using fast Fourier ...
One-dimensional thermodynamic instabilities are phase transitions, not prohibited by Landaus argument because the energy of the domain wall which separates the two phases is infinite. Whether they actually occur in a given system of particles must be demonstrated on a case-by-case basis by examining the properties of the corresponding singular transfer integral (TI) equation. The present work deals with the generic Peyrard-Bishop model of DNA denaturation. In the absence of exact statements about the spectrum of the singular TI equation, I use Gauss-Hermite quadratures to achieve a single-parameter-controlled approach to rounding effects; this allows me to employ finite-size scaling concepts in order to demonstrate that a phase transition occurs and to derive the critical exponents.
Abstract: Supposing there exists no new physics stabilizing the weak scale, the Standard Model Higgs potential exhibits a true vacuum at large field values, rendering the electroweak vacuum metastable (i.e., long lived relative to the age of the Universe). While this scenario need not preclude our current existence, it may not reconcile with a period of large(ish)-field inflation---large fluctuations in the Higgs field, induced by the inflationary energy density, can lead to the field locally sampling the unstable/true vacuum part of the potential, with potentially disastrous consequences. Evaluating the extent to which large-field inflation and the Higgs vacuum instability are incompatible requires understanding (i) how Higgs fluctuations evolve during inflation and (ii) the fate of large local fluctuations that sample the part of the potential beyond the barrier that separates the electroweak and true vacua. In this talk, I will discuss both of these aspects, and explain the implications for ...
Instabilities in polymer processing limit production rates and may influence to some degree the optical or mechanical properties of the final product. One prominent example is the fountain flow instability, which takes place during the mold filling stage of an injection molding process. Old car bumpers which show light and dark lines are a famous example of an injection molded part in which such an instability occurred.
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is negative, one expects curvature instabilities of the membrane and, in turn, these instabilities generate a pattern of domains that differ both in composition and in local curvature. Scaling arguments motivate the study of the family of singular perturbed energies ...
Strategies the pa- tient has used to reduce risk for infection are identified.1994; Zwangersschap and Shine, 1992; Mishima et al.
that instability can occur even after the full establishment of the primary flow. Chandrasekhars method is used in the analysis and the relationship between the stability parameter and the wave number of the disturbance for neutral stability is obtained."--Page 1 ...
2019 marks a year of instability and uncertainty reflected in the field of potential best picture nominees, from Parasite to Joker.
In the present study, we found that the centrosomes in nearly all pancreatic ductal carcinomas displayed structural abnormalities, such as an increase in their number and size, and an irregular distribution. Quantitative analysis demonstrated a significant difference in centrosome number between normal and cancer cells. In addition, double-labeled immunofluorescence analysis of MIA PaCa-2 pancreatic cancer cells suggest that these aberrant centrosomes contribute to the assembly of multipolar spindles, which may result in the improper segregation of chromosomes during mitosis. These results are consistent with previous studies describing centrosome abnormalities in human malignant tumors of the breast, prostate, brain, lung, and colon (10 , 11) . To our knowledge, however, this is the first report to demonstrate centrosome abnormalities in pancreatic carcinoma.. The centrosome plays a key role in the organization of cytoplasmic microtubules, in the determination of cell polarity, and in the ...
Cells have intrinsic mechanisms that facilitate centrosome clustering (Godinho and Pellman, 2014). Thus, it is thought that cells are unlikely to require adaptation to centrosome amplification, which is further supported by the fact that most cancer cell lines with extra centrosomes are able to cluster centrosomes efficiently (Ring et al., 1982; Quintyne et al., 2005; Kwon et al., 2008; Ganem et al., 2009). However, our findings challenge this idea and indicate that at least in epithelial tumors, cancer cells need to adapt to efficiently proliferate in the presence of supernumerary centrosomes. We demonstrate that induction of centrosome amplification in a panel of nontransformed cell lines reveals intrinsic differences in clustering ability, with epithelial cells displaying an inefficient process. These differences are not caused by centrosome inactivation, as previously shown in Drosophila cells with extra centrosomes (Sabino et al., 2015), highlighting that the prevalence of mechanisms that ...
Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than two centrosomes. This death program can occur after ...
3197 Cyclin E, a regulatory subunit of CDK2 has key S phase promoting functions in normal cells. Cyclin E is often overexpressed and present in low molecular weight (LMW) isoforms in malignant cells and such deregulation is associated with aggressive disease and poor outcome. Stable overespression of LMW cyclin E in breast cancer cells promotes chromosome instability in breast cancer cells. Examination of human cancer tissues and cultured cells has revealed a significant correlation between loss and/or mutation of tumor suppressor p53 and occurrence of centrosome amplification. We hypothetized that cyclin E LMW overexpression together with p53 depletion, cooperate to efficiently induce spindles abnormalities and centrosome amplification leading to chromosomal instability. To test this hypothesis we generated a model system composed of MCF-7 cells, which inducibly overexpress the LMW cyclin E protein under control of tetracycline-inducible promoter. Short-term induction of LMW of cylin E for 24 ...
Genetic and Molecular Basis of Chromosome Instability. Funded by: Canadian Cancer Society Research Institute, Ontario Government Early Research Award, NSERC Discovery Award.. Scientists have found chromosome gain or loss in nearly all major human tumour types. Dr. Baetzs current research project involves developing and implementing yeast chemical and functional genomic screens in order to identify networks of proteins required for chromosome stability in S. cerevisiae. Once the proteins that are required for chromosome stability are identified, she and her research team uses traditional methods drawn from biochemistry and molecular biology to reveal the molecular mechanisms used by these proteins to prevent chromosome loss. Considering the conservation between yeast and human processes governing chromosome segregation, the Baetz laboratorys research with yeast will be of directly relevance to human cancer biology, and will provide new insights into the molecular mechanism of chromosomal ...
Tumors are dynamic organs that evolve during disease progression with genetic, epigenetic, and environmental differences among tumor cells serving as the foundation for selection and evolution in tumors. Tumor-initiating cells (TIC) that are responsible for tumorigenesis are a source of functional cellular heterogeneity, whereas chromosomal instability (CIN) is a source of karyotypic genetic diversity. However, the extent that CIN contributes to TIC genetic diversity and its relationship to TIC function remains unclear. Here, we demonstrate that glioblastoma TICs display CIN with lagging chromosomes at anaphase and extensive nonclonal chromosome copy-number variations. Elevating the basal chromosome missegregation rate in TICs decreases both proliferation and the stem-like phenotype of TICs in vitro. Consequently, tumor formation is abolished in an orthotopic mouse model. These results demonstrate that TICs generate genetic heterogeneity within tumors, but that TIC function is impaired if the ...