Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations.

ABSTRACT: Cancer driver genes can undergo positive selection for various types of genetic alterations, including gain-of-function or loss-of-function mutations and copy number alterations (CNA). We investigated the landscape of different types of alterations affecting driver genes in 17,644 cancer exomes and genomes. We find that oncogenes may simultaneously exhibit signatures of positive selection and also negative selection in different gene segments, suggesting a method to identify additional tumor types where an oncogene is a driver or a vulnerability. Next, we characterize the landscape of CNA-dependent selection effects, revealing a general trend of increased positive selection on oncogene mutations not only upon CNA gains but also upon CNA deletions. Similarly, we observe a positive interacti

SUBMITTER: Besedina E 

PROVIDER: S-EPMC11271286 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature