Differential analysis between somatic mutation and germline variation profiles reveals cancer-related genes

Genome Med. 2017 Aug 25;9(1):79. doi: 10.1186/s13073-017-0465-6.


A major aim of cancer genomics is to pinpoint which somatically mutated genes are involved in tumor initiation and progression. We introduce a new framework for uncovering cancer genes, differential mutation analysis, which compares the mutational profiles of genes across cancer genomes with their natural germline variation across healthy individuals. We present DiffMut, a fast and simple approach for differential mutational analysis, and demonstrate that it is more effective in discovering cancer genes than considerably more sophisticated approaches. We conclude that germline variation across healthy human genomes provides a powerful means for characterizing somatic mutation frequency and identifying cancer driver genes. DiffMut is available at https://github.com/Singh-Lab/Differential-Mutation-Analysis .

Keywords: Cancer; Cancer driver genes; Germline variation; Somatic mutations; Whole-exome sequencing.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Mutational Analysis / methods*
  • Exome
  • Female
  • Genes, Neoplasm*
  • Genetic Predisposition to Disease
  • Genomics / methods
  • Germ-Line Mutation*
  • Humans
  • Male
  • Mutation*
  • Neoplasms / genetics*
  • Polymorphism, Genetic
  • Software