Comprehensive Characterization of Cancer Driver Genes and Mutations

The MC3 Working Group, The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

Abstract

Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%–85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors. A comprehensive analysis of oncogenic driver genes and mutations in >9,000 tumors across 33 cancer types highlights the prevalence of clinically actionable cancer driver events in TCGA tumor samples.

Original languageEnglish (US)
Pages (from-to)371-385.e18
JournalCell
Volume173
Issue number2
DOIs
StatePublished - Apr 5 2018

Fingerprint

Neoplasm Genes
Tumors
Genes
Mutation
Neoplasms
Blueprints
Oncology
Ports and harbors
Exome
Atlases
Missense Mutation
Genome

Keywords

  • driver gene discovery
  • mutations of clinical relevance
  • oncology
  • structure analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The MC3 Working Group, & The Cancer Genome Atlas Research Network (2018). Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell, 173(2), 371-385.e18. https://doi.org/10.1016/j.cell.2018.02.060

Comprehensive Characterization of Cancer Driver Genes and Mutations. / The MC3 Working Group; The Cancer Genome Atlas Research Network.

In: Cell, Vol. 173, No. 2, 05.04.2018, p. 371-385.e18.

Research output: Contribution to journalArticle

The MC3 Working Group & The Cancer Genome Atlas Research Network 2018, 'Comprehensive Characterization of Cancer Driver Genes and Mutations', Cell, vol. 173, no. 2, pp. 371-385.e18. https://doi.org/10.1016/j.cell.2018.02.060
The MC3 Working Group, The Cancer Genome Atlas Research Network. Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell. 2018 Apr 5;173(2):371-385.e18. https://doi.org/10.1016/j.cell.2018.02.060
The MC3 Working Group ; The Cancer Genome Atlas Research Network. / Comprehensive Characterization of Cancer Driver Genes and Mutations. In: Cell. 2018 ; Vol. 173, No. 2. pp. 371-385.e18.
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