Dna mutational analysis. Medical search. Frequent questions

StrataNGS includes actionable DNA and RNA biomarkers and will be expanded to include tumor mutational load. (pharmiweb.com)
Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better? (aacrjournals.org)
High tumor mutational burden (TMB-H) has shown promise as a biomarker in lung cancer, but the broad applicability of TMB-H as a biomarker of response across all solid tumors is unclear. (aacrjournals.org)
The FDA has approved the programmed cell death protein-1 (PD-1) inhibitor, pembrolizumab, in solid tumors with a tumor mutational burden (TMB) ≥ 10 mutations/megabase based on the FoundationOne CDx assay. (aacrjournals.org)
On June 16, 2020, the FDA approved the programmed cell death protein-1 (PD-1) inhibitor, pembrolizumab (KEYTRUDA, Merck & Co., Inc.), for the treatment of tumor mutational burden-high (TMB-H) solid tumors. (aacrjournals.org)

TMB is defined as the number of somatic mutations/megabase whereas mutational signatures are distinct mutational patterns of single base substitutions, double base substitutions, or small insertions and deletions in tumors. (wikipedia.org)
However, while DNA repair is often deficient in tumors, many DNA repair genes such as MLH1 , MGMT , BRCA1, or ATM do not commonly bear somatic mutations. (nature.com)
RESULTS: All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. (lu.se)
Double and triple mutants F16W/I24Q, F16W/N27D, and F16W/I24Q/N27D all showed defects in DNA binding, strand transfer, and helix destabilization, suggesting that the I24Q and N27D mutations have a "dominant negative" effect and abolish the positive influence of F16W. (umd.edu)
Tumor cells from patients with acquired resistance were examined for secondary EGFR kinase domain mutations by molecular analyses. (aacrjournals.org)
Deletions were analyzed by long range PCR, point mutations by heteroduplex analysis of the D-loop region, and copy number changes by real-time PCR. (maastrichtuniversity.nl)
Standard methods sequence DNA that has been extracted from a population of cells, such that not only the genetic composition of individual cells is lost, but also de novo mutations in cell(s) are effectively concealed by the bulk signal. (sanger.ac.uk)
Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). (uni-muenchen.de)
Consistent with the absence of identified mutations, linkage analysis excluded linkage of the mutant phenotypes to crx. (zfin.org)
Most studies in this context have focused on an inherently additive analysis, e.g. by non-negative matrix factorization, where the mutations within a cancer sample are explained by a linear combination of independent mutational signatures. (aalto.fi)
G1138A and G1138C mutations of FGFR3 account for 99% of the mutational changes in patients with achondroplasia. (medscape.com)
A mutational signature of aristolochic acid was observed in the tumour DNA, and the principal aristolochic acid-specific mutation spectra and deleterious mutations were present in the mRNA of up to 50% of genes that were active in tumours. (who.int)
Human cancer genome sequencing studies have generated ample, publicly available data, and analyses of these data have substantially broadened the knowledge of somatic mutations accumulating in tumours. (who.int)
Most of these mutations change single DNA building blocks (nucleotides) in the gene. (medlineplus.gov)
Notre étude a démontré que les mutations du gène HFE sont fréquentes en Égypte chez les porteurs d'une -thalassémie par rapport aux sujets témoins. (who.int)

The package provides functionalities for both extracting mutational signatures de novo and determining the contribution of previously identified mutational signatures on a single sample level. (bioconductor.org)

Tumour mutational burden (abbreviated as TMB) is a genetic characteristic of tumorous tissue that can be informative to cancer research and treatment. (wikipedia.org)
This package provides a comprehensive set of flexible functions that allows researchers to easily evaluate and visualize a multitude of mutational patterns in base substitution catalogues of e.g. healthy samples, tumour samples, or DNA-repair deficient cells. (bioconductor.org)

In addition to gene expression, mutational signatures-readouts of genome instability-can characterize DNA repair deficiencies. (nature.com)
Pif1 is a multifunctional helicase and DNA processing enzyme that has roles in genome stability. (rcsb.org)
Single-cell genome analyses overcome these issues. (sanger.ac.uk)
We are developing single-cell genome sequencing technologies to enable the discovery of the entire spectrum of DNA mutation -including the acquisition of ploidy changes, aneuploidies, copy number variants, structural variants, retrotranspositions, indels, and single nucleotide variants. (sanger.ac.uk)
But FDA's findings are potentially trivial besides another recent discovery about gene-editing: that foreign DNA from surprising sources can routinely find its way into the genome of edited animals. (greenmedinfo.com)
Ultimately, all DNA 'editing' is really the cutting of DNA by enzymes, called nucleases, that are supposed to act only at chosen sites in the genome of a living cell. (greenmedinfo.com)
To understand what causes chondrodysplasia, a team of researchers led by Dr. Elaine Ostrander of NIH's National Human Genome Research Institute (NHGRI) examined DNA samples from 835 dogs from 76 distinct breeds, including 95 dogs from 8 breeds with short legs. (nih.gov)
Through follow-up DNA sequencing and computational analyses, they found that the dogs' short limbs can be traced to one mutational event in the canine genome-a DNA insertion-that occurred early in the evolution of domestic dogs, some time after the ancestor of modern dog breeds diverged from wolves. (nih.gov)
The new DNA can be inserted into the genome, usually at a different place than the original gene. (nih.gov)
Genome-wide linkage screen with 10 k SNP microarray, fine mapping with microsatellite markers, and mutational analysis of the genomic DNA were performed on the pedigree. (bmj.com)
A considerable fraction of the compendium of mutational signatures extracted from cancer genome sequencing studies remains without etiological explanation, and mutational signatures alone may be insufficient in explaining cancer causes. (who.int)
The MUTSPEC 2.0 project was developed to accommodate a highly integrated design to identify mutational (and other toxicogenomic) signatures of carcinogens derived by genome-scale sequencing analysis of mutually complementary and cross-validating systems. (who.int)

We detect mutational signatures in cancer cell line exomes (where matched healthy tissues are not available) by adjusting for the confounding germline mutation spectra across ancestries. (nature.com)
The technology will answer burning questions on mutational burden in normal development and how this is impacted by germline genetic background, lifestyle, aging and disease. (sanger.ac.uk)

Due to the advancement of genomic analysis, a vast literature characterizing cancer-associated molecular aberrations and relative therapeutic relevance has been published. (nih.gov)
Through this analysis, we have identified patient indications, molecular aberrations, and targeted therapy classes that have strong or weak representation in clinical trials. (nih.gov)
Because of the above, other types of molecular markers may be more useful to infer about failed DNA repair. (nature.com)
Launch the Pan-cancer molecular Analysis for cancer THerapy (PATH) study, a Strata-sponsored master therapeutic protocol, to support rapid and cost-effective indication expansion studies for on-market pharma drugs. (pharmiweb.com)
An integrative analysis of the transcriptome, epigenome and proteome of distinct TEC subpopulations will be used to attain an unparalleled systems-level understanding of the molecular conditions that select a tolerant T cell repertoire under normal physiological conditions. (sanger.ac.uk)
The methods for tissue fixation currently used in traditional histology are of limited use for molecular analysis. (qiagen.com)
PAXgene Tissue reagents in prefilled containers and PAXgene Tissue Kits provide a complete preanalytical solution for collection, fixation, and stabilization of tissue, and purification of high-quality nucleic acids for molecular research analysis. (qiagen.com)
Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. (spandidos-publications.com)
hence, molecular testing by targeted mutational analysis is easily done and interpreted. (medscape.com)
C.P. tion stage, why much more detailed molecular analysis is contributed to the design of the study, discussions on statistical analysis of called for [2]. (lu.se)

Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. (uni-muenchen.de)

Thermal unfolding studies of cold adapted uracil-DNA N-glycosylase (UNG) from Atlantic cod (Gadus morhua). (uit.no)

Mitochondrial DNA (mtDNA) is more susceptible to oxidative damage than nuclear DNA. (maastrichtuniversity.nl)
The mutational analysis of mitochondrial DNA in maternal inheritance of polycystic ovarian syndrome. (cdc.gov)

Pathogenicity assessment of PMS2 VUS was performed evaluating clinicopathological data, frequency in control population and in silico and in vitro analyses at the RNA and protein level. (bmj.com)
In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. (hindawi.com)

These challenges further complicate analyses designed to elucidate biomarkers and mechanisms associated with treatment response. (wustl.edu)

Once again, we used genomic and transcriptomic analyses to characterize the mutational landscapes of these patient cohorts. (wustl.edu)

Previous studies identified that both DAB2 and DAB2IP genes were inactivated by promoter hypermethylation in human cancers, but their mutational alterations in cancers remain largely unknown. (nih.gov)
The aim of our study was to find whether DAB2 and DAB2IP were mutated in gastric (GCs) and colorectal cancers (CRCs) by DNA sequencing. (nih.gov)
Results: We carefully analysed such additive model fits from the PCAWG study cataloguing mutational signatures as well as their activities across thousands of cancers. (aalto.fi)
Ethanol's main metabolite acetaldehyde (AcA) may play a crucial role in head and neck cancers by forming covalent DNA adducts that can be mutagenic and may contribute to cancer development. (who.int)

Genomic analyses have revealed mutational footprints associated with DNA maintenance gone awry, or with mutagen exposures. (nature.com)
Mutational processes leave characteristic footprints in genomic DNA. (bioconductor.org)

This is exemplified by a mutational signature associated with pathogenic variants in BRCA1 and BRCA2 genes 11 , 23 , thus identifying HR deficient tumors. (nature.com)
The aim of this study was to evaluate the role of PMS2 in LS by assessing the pathogenicity of variants of unknown significance (VUS) detected in the mutational analysis of PMS2 in a series of Spanish patients. (bmj.com)
Results Overall 25 different PMS2 DNA variants were detected. (bmj.com)
Genomic DNA was isolated and amplified using nature for these variants. (cdc.gov)

The package covers a wide range of patterns including: mutational signatures, transcriptional and replicative strand bias, lesion segregation, genomic distribution and association with genomic features, which are collectively meaningful for studying the activity of mutational processes. (bioconductor.org)
We propose an extension to the additive mutational signature model-multiplicatively acting modulatory processes-and develop a maximum-likelihood framework to identify such modulatory mutational signatures. (aalto.fi)
Conclusion: We suggest the modulatory processes biologically relate to sample specific DNA repair propensities with cancer or tissue type specific profiles. (aalto.fi)
We observed mutation patterns (COSMIC signature SBS17) consistent with a possible role oxidative DNA damage processes linked to inflammation and cell keratinization. (who.int)
Analysis of mutational signatures focuses on how characteristic somatic DNA mutation patterns reflect the contributions of particular mutagenic processes to cancer development, and it is thus of key importance for cancer etiology and carcinogen exposure studies. (who.int)

Each of Recombinetics' calves possessed two antibiotic resistance genes, along with other segments of superfluous bacterial DNA. (greenmedinfo.com)
Analysis is in progress to map these loci and identify the genes responsible for the retinal degeneration phenotype in these mutant lines. (zfin.org)
The scientists noted that, although functional, the extra gene lacks certain parts of the DNA code, called introns, found in normal genes. (nih.gov)

Dr. Tao Xie is currently affiliated to Pfizer Global Research and Development, USA, continuing research in the specialized scientific area of Gene dosage, Oncogenes, Tumor cell line, DNA mutational analysis, DNA methylation, Gene expression profiling. (iomcworld.com)

While both TMB and mutational signatures give us critical information about cancer behaviour, they have different definitions. (wikipedia.org)
Because cancer therapeutics often target DNA synthesis or repair, we asked if mutational signatures make useful markers of drug sensitivity. (nature.com)
Many commonly employed cancer drugs act by interfering with DNA synthesis or maintenance or by damaging DNA. (nature.com)
Therefore, the altered capacity of cancer cells to repair and/or replicate DNA is the basis of many classical therapies, such as platinum-based agents, and also recently introduced or upcoming therapies, such as PARP inhibitors or ATR inhibitors (reviewed in refs. (nature.com)
It is paramount to identify predictive markers that are associated with failures of DNA maintenance in cancer cells. (nature.com)
Because mutational signatures describe the state of the DNA repair machinery of a cancer cell, they may be able to serve as a drug sensitivity marker. (nature.com)
Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer. (cancerindex.org)
The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. (cancerindex.org)
Background: A deep understanding of carcinogenesis at the DNA level underpins many advances in cancer prevention and treatment. (aalto.fi)
Next generation sequencing, especially of DNA and RNA, has been rapidly integrated into preclinical and clinical cancer research. (wustl.edu)
We hypothesized that the role of AcA in alcohol-related oral cancer is based on the formation of specific mutational signature(s) which can be identified in suitable experimental systems. (who.int)
PCAWG, Pan-Cancer Analysis of Whole Genomes. (who.int)

RESULTS: The analysis indicated that the zebrafish crx gene consisted of three exons and 2 introns, and spans 3.8 kb of genomic DNA. (zfin.org)

[ 13 ] About 98% of diagnosed patients have the G1138A mutation, resulting in a G-to-A DNA nucleotide point change. (medscape.com)
One percent of cases have a G-to-C DNA point change at nucleotide 1138, causing the G1138C mutation. (medscape.com)

PAXgene Tissue Kits and supplementary protocols provide efficient subsequent purification of RNA, miRNA, DNA, and/or proteins from the same sample. (qiagen.com)
Retrogenes arise from molecules called messenger RNA (mRNA), which are copies of a gene's DNA code that the cell needs in order to make proteins. (nih.gov)

GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. (lu.se)

The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. (spandidos-publications.com)

Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. (umassmed.edu)
Structural differences, in particular in the DNA strand separation wedge region, highlight significant evolutionary divergence of the human PIF1 protein from bacterial and yeast orthologues. (rcsb.org)

Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. (jnccn.org)
This approval was based on an exploratory analysis of the KEYNOTE-158 study, which was a single-arm, phase II multi-cohort study of pembrolizumab for select, previously treated advanced solid tumors. (aacrjournals.org)
These analyses addressed challenges related to tumor purity and the presence of nontumor cell populations by quantifying and characterizing the microenvironmental cell populations and dynamics in primary tumors. (wustl.edu)

In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. (unige.ch)

Replication analyses across independent drug and CRISPR genetic screening data sets reveal hundreds of robust associations, which are provided as a resource for drug repurposing guided by mutational signature markers. (nature.com)
The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (nature.com)
The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. (nature.com)
In the budding yeast Saccharomyces cerevisiae , there are over 400 origins of DNA replication located on 16 chromosomes and they can function as autonomously replicating sequences (ARSs) when inserted into a plasmid 19 . (nature.com)
The ORC-Cdc6 complex (product 1) assembles in step 1 around origin DNA and with the help of another replication initiator protein, Cdt1, it recruits the Mcm2-7 hexamer to the origin in step 2. (nature.com)

Viral packaging ATPases utilize a glutamate switch to couple ATPase activity and DNA translocation. (umassmed.edu)

Comprehensive Mutational Analysis of the BRCA1-Associated DNA Helicase and Tumor-Suppressor FANCJ/BACH1/BRIP1. (umassmed.edu)

Mutational analysis suggests that while the ssDNA-binding channel is important for helicase activity, it is not used in DNA annealing. (rcsb.org)

The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. (nature.com)

The scientists surveyed more than 40,000 markers of DNA variation. (nih.gov)

Apart from wet-lab approaches, we also develop the computational means for the analysis of single cells. (sanger.ac.uk)

Comparisons with the structures of yeast and bacterial Pif1 reveal a conserved ssDNA binding channel in hPIF1 that we show is critical for single-stranded DNA binding during unwinding, but not the binding of G quadruplex DNA. (rcsb.org)

MutationalPatterns integrates with common R genomic analysis workflows and allows easy association with (publicly available) annotation data. (bioconductor.org)

Colibactin's distinct mutational signature is reflected in human CRC, suggesting a causal link. (uni-muenchen.de)

Neighbor-Joining, Maximum Parsimony and Maximum Likelihood analysis revealed Jakun and Semelai haplotypes are the earliest to split from ingroups and showed that Jakun may be an ancestor for the Malay populations in the Malay Peninsular, which also support the anthropological findings. (scialert.net)

Analysis of copy number variation in AZF region of Y chromosome in patients with spermatogenic failure]. (cdc.gov)
Mutational analysis of 105 mucopolysaccharidosis type VI patients. (medlineplus.gov)

Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions. (umassmed.edu)
However, other recent studies show that the mutational signatures exhibit non-additive interactions. (aalto.fi)

This genetic material is not DNA that was put there on purpose, but rather, is a contaminant of standard editing procedures. (greenmedinfo.com)
Linkage analysis used DNA from mapping panels of single homozygous mutant animals with mixed genetic backgrounds. (zfin.org)

In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. (cancerindex.org)
However, these approaches were more specifically designed to relate the mutational and gene expression landscapes to clinical and pathologic responses to treatment. (wustl.edu)

Overall, our results identify an interesting direction where to expand signature analysis. (aalto.fi)

Thus, apparently unbeknownst to Recombinetics, adjacent to its edited site were 4,000 base pairs of DNA that originated from the plasmid vector used to introduce the DNA required for the hornless trait. (greenmedinfo.com)
The origin of this foreign DNA, as with Recombinetics' calves, was the plasmid vector used in the editing process. (greenmedinfo.com)

We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. (hindawi.com)

For most commercial applications gene-editing's appeal is simplicity and precision: it alters genomes at precise sites and without inserting foreign DNA. (greenmedinfo.com)
Mutational signatures are identified in the genomes of the rat tumours and exposed cells, and are matched with the pre-mutagenic DNA lesions identified by LC-MS/MS DNA adductomic analysis of the cell exposure models. (who.int)
The analysis of AcA exposure impact on the cell line genomes is underway and will be integrated with AcA-induced DNA adductome analyses. (who.int)

The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. (spandidos-publications.com)
Formalin‑fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. (spandidos-publications.com)

The comprehensive functional analysis shown here has been useful in the classification of PMS2 VUS and contributes to refining the role of PMS2 in LS. (bmj.com)

The application included interim analyses of a phase1/2 and a bridging study conducted in China, and a phase 3 study conducted in the United Arab Emirates and other Arab countries. (who.int)

Anatomy11

Organisms17

Diseases2

Chemicals and Drugs89

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes94

Information Science3

Tumor mutational5

Mutations15

Identified mutational signatures1

Tumour2

Genome12

Germline2

Molecular10

Burden1

Uracil-DNA N-glycosylase1

Mitochondrial2

Vitro analyses2

Biomarkers1

Characterize1

Cancers4

Footprints2

Variants4

Processes5

Genes3

Methylation1

Cancer12

Exons1

Nucleotide2

Proteins2

Flow cytometry1

Adenocarcinoma1

Structural2

Tumors3

Alterations1

Replication5

Translocation1

BRCA11

Helicase1

Reveals1

Markers1

Computational1

Single-stranded1

Genomic analysis1

Distinct1

Maximum Likelihood1

Patients2

Interactions2

Genetic2

Clinical2

Signature1

Plasmid2

Cohort1

Genomes3

Mutation analysis2

Functional1

Study1