Cancer gene mutation frequencies for the U.S. population

Gaurav Mendiratta (), Eugene Ke (), Meraj Aziz, David Liarakos, Melinda Tong and Edward C. Stites ()
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Gaurav Mendiratta: Salk Institute for Biological Studies
Eugene Ke: Immunology, and Cancer, School of Medicine, University of Virginia
Meraj Aziz: Salk Institute for Biological Studies
David Liarakos: Salk Institute for Biological Studies
Melinda Tong: Salk Institute for Biological Studies
Edward C. Stites: Salk Institute for Biological Studies

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26213-y

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