Reannotation of cancer mutations based on expressed RNA transcripts reveals functional non-coding mutations in melanoma.

ABSTRACT: The role of synonymous mutations in cancer pathogenesis is currently underexplored. We developed a method to detect significant clusters of synonymous and missense mutations in public cancer genomics data. In melanoma, we show that 22% (11/50) of these mutation clusters are misannotated as coding mutations because the reference transcripts used for their annotation are not expressed. Instead, these mutations are actually non-coding. This, for instance, applies to the mutation clusters targeting known cancer genes kinetochore localized astrin (SPAG5) binding protein (KNSTRN) and BCL2-like 12 (BCL2L12), each affecting 4%-5% of melanoma tumors. For the latter, we show that these mutations are functional non-coding mutations that target the shared promoter region of interferon regulatory facto

SUBMITTER: Pepe D 

PROVIDER: S-EPMC12256795 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature