Mutational landscape and significance across 12 major cancer types

Mutational landscape and significance across 12 major cancer types

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 Pa...

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Main Authors: 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
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/
id pubmed-3927368
recordtype oai_dc
spelling pubmed-39273682014-02-18 Mutational landscape and significance across 12 major cancer types 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 Article 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(forexample, mitogen-activatedprotein kinase, phosphatidylinositol-3-OH kinase,Wnt/β-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 numberof 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. 2013-10-17 /pmc/articles/PMC3927368/ /pubmed/24132290 http://dx.doi.org/10.1038/nature12634 Text en This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported licence. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-sa/3.0
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author 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
spellingShingle 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
Mutational landscape and significance across 12 major cancer types
author_facet 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
author_sort Kandoth, Cyriac
title Mutational landscape and significance across 12 major cancer types
title_short Mutational landscape and significance across 12 major cancer types
title_full Mutational landscape and significance across 12 major cancer types
title_fullStr Mutational landscape and significance across 12 major cancer types
title_full_unstemmed Mutational landscape and significance across 12 major cancer types
title_sort mutational landscape and significance across 12 major cancer types
description 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(forexample, mitogen-activatedprotein kinase, phosphatidylinositol-3-OH kinase,Wnt/β-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 numberof 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.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/
_version_ 1612059414969188352

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