Publikationsdatum:
2013-10-18
Beschreibung:
The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known (for example, mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, Wnt/beta-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the number of driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kandoth, Cyriac -- McLellan, Michael D -- Vandin, Fabio -- Ye, Kai -- Niu, Beifang -- Lu, Charles -- Xie, Mingchao -- Zhang, Qunyuan -- McMichael, Joshua F -- Wyczalkowski, Matthew A -- Leiserson, Mark D M -- Miller, Christopher A -- Welch, John S -- Walter, Matthew J -- Wendl, Michael C -- Ley, Timothy J -- Wilson, Richard K -- Raphael, Benjamin J -- Ding, Li -- P01 CA101937/CA/NCI NIH HHS/ -- P01CA101937/CA/NCI NIH HHS/ -- R01 CA180006/CA/NCI NIH HHS/ -- R01 HG005690/HG/NHGRI NIH HHS/ -- R01CA180006/CA/NCI NIH HHS/ -- R01HG005690/HG/NHGRI NIH HHS/ -- U01 HG006517/HG/NHGRI NIH HHS/ -- U01HG006517/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- England -- Nature. 2013 Oct 17;502(7471):333-9. doi: 10.1038/nature12634.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Institute, Washington University in St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132290" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Carcinogenesis/*genetics
;
Cell Cycle/genetics
;
Clone Cells/metabolism/pathology
;
Cohort Studies
;
DNA Repair/genetics
;
Humans
;
INDEL Mutation/genetics
;
Mitogen-Activated Protein Kinases/genetics
;
Models, Genetic
;
Mutation/*genetics
;
Neoplasms/*classification/*genetics/metabolism/pathology
;
Oncogenes/genetics
;
Phosphatidylinositol 3-Kinases/genetics
;
Point Mutation/genetics
;
Receptor Protein-Tyrosine Kinases/metabolism
;
Survival Analysis
;
Time Factors
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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