Cell
Volume 173, Issue 2, 5 April 2018, Pages 371-385.e18
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Article
Comprehensive Characterization of Cancer Driver Genes and Mutations

https://doi.org/10.1016/j.cell.2018.02.060Get rights and content
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open access

Highlights

  • PanSoftware applied to PanCancer data identified 299 cancer driver genes

  • Driver genes and mutations are shared across anatomical origins and cell types

  • In silico discovery of ∼3,400 driver mutations coupled with experimental validation

  • 57% of tumors harbor potentially actionable oncogenic events

Summary

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.

Keywords

oncology
driver gene discovery
structure analysis
mutations of clinical relevance

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31

These authors contributed equally

32

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