The Frequency of Ras Mutations in Cancer

Abstract

Ras is frequently mutated in cancer, however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10%-30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. To provide a more definitive figure for Ras mutation frequency in cancer, we cross-referenced the data in all major publicly accessible cancer mutation databases to determine reliable mutation frequency values for each Ras isoform in all major cancer types. These percentages were then applied to current U.S. cancer incidence statistics to estimate the number of new patients each year that have Ras-mutant cancers. We find that approximately 19% of patients with cancer harbor Ras mutations, equivalent to approximately 3.4 million new cases per year worldwide. We discuss the Ras isoform and mutation-specific trends evident within the datasets that are relevant to current Ras-targeted therapies.

Figure 1.. Overview of Ras data in cancer genetics databases.

A. The sampling relationship, the number of samples tested, and the number of Ras mutant samples identified in each of the publicly accessible databases and data portals. B. The sample tissue composition of each database is not equivalent. Data sources: COSMIC v85, cBioPortal v2.2.0, ICGC release 27, TCGA release 12.0 all accessed contemporaneously.