Comprehensive Characterization of Cancer Driver Genes and Mutations

Cell. Volume 173, Issue 2 p371-385.e18, 5 April 2018 10.1016/j.cell.2018.02.060

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 The Cancer Genome Atlas projects) and using 26 computational tools to catalogue 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.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (23 Files)

Supplemental Data

• Project Tools
  • 2020plus gene discovery tool - 2020plus.tar.gz
  • 3DHotSpots mutation discovery tool - 3DHotSpots.org.tar.gz
  • ActiveDriver gene discovery tool - ActiveDriver.tar.gz
  • CHASM mutation discovery tool - CHASM.tar.gz
  • CanDrA mutation discovery tool - CanDrA.tar.gz
  • CompositeDriver gene discovery tool - CompositeDriver.tar.gz
  • DriverNet gene discovery tool - DriverNet.tar.gz
  • HotMAPS mutation discovery tool - HotMAPS.tar.gz
  • HotSpot3D mutation discovery tool - HotSpot3D.tar.gz
  • MuSiC gene discovery tool - MuSiC.tar.gz
  • MutSig2CV gene discovery tool - MutSig2CV.tar.gz
  • MutationAssessor mutation discovery tool - MutationAssessor.tar.gz
  • OncoIMPACT gene discovery tool - OncoIMPACT.tar.gz
  • OncodriveCLUST gene discovery tool - OncodriveCLUST.tar.gz
  • OncodriveFML gene discovery tool - OncodriveFML.tar.gz
  • PolyPhen2 mutation discovery tool - PolyPhen2.tar.gz
  • SIFT mutation discovery tool - SIFT.tar.gz
  • VEST mutation discovery tool - VEST.tar.gz
  • e-Driver gene discovery tool - e-Driver.tar.gz
  • e-Driver3D mutation discovery tool - e-Driver3D.tar.gz
  • fathmm mutation discovery tool - fathmm.tar.gz
  • transFIC mutation discovery tool - transFIC.tar.gz
  • Mutation Scores and tool aggregation - Mutation.CTAT.3D.Scores.txt

Additional Resources

• Broad Institute FireCloud (link is external) The Broad Institute
• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
• PanCanAtlas Additional Files