Cancer gene mutation frequencies for the U.S. population

Nat Commun. 2021 Oct 13;12(1):5961. doi: 10.1038/s41467-021-26213-y.

Abstract

Mutations play a fundamental role in the development of cancer, and many create targetable vulnerabilities. There are both public health and basic science benefits from the determination of the proportion of all cancer cases within a population that include a mutant form of a gene. Here, we provide the first such estimates by combining genomic and epidemiological data. We estimate KRAS is mutated in only 11% of all cancers, which is less than PIK3CA (13%) and marginally higher than BRAF (8%). TP53 is the most commonly mutated gene (35%), and KMT2C, KMT2D, and ARID1A are among the ten most commonly mutated driver genes, highlighting the role of epigenetic dysregulation in cancer. Analysis of major cancer subclassifications highlighted varying dependencies upon individual cancer drivers. Overall, we find that cancer genetics is less dominated by high-frequency, high-profile cancer driver genes than studies limited to a subset of cancer types have suggested.

Publication types

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

MeSH terms

  • Computational Biology / methods
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic
  • Genetics, Population
  • Humans
  • Incidence
  • Mutation Rate*
  • Neoplasm Proteins / classification
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / classification
  • Neoplasms / epidemiology*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Terminology as Topic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • United States / epidemiology

Substances

  • ARID1A protein, human
  • DNA-Binding Proteins
  • KMT2C protein, human
  • KMT2D protein, human
  • KRAS protein, human
  • Neoplasm Proteins
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)