{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["112(6)"],"submitter":["Pepe D"],"pubmed_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"],"journal":["American journal of human genetics"],"pagination":["1447-1467"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12256795"],"repository":["biostudies-literature"],"pubmed_title":["Reannotation of cancer mutations based on expressed RNA transcripts reveals functional non-coding mutations in melanoma."],"pmcid":["PMC12256795"],"pubmed_authors":["Godderis A","Cabrerizo Granados D","Konstantakos V","De Groote D","Kampen KR","Dewaele B","Royaert J","Marron-Linares GM","Pepe D","Timcheva K","Menschaert G","Verhasselt A","Cools C","Subramanian K","Franco-Tolsau M","De Keersmaecker K","De Bie J","Verbeeck J","Janssens X","Verbelen B"],"additional_accession":[]},"is_claimable":false,"name":"Reannotation of cancer mutations based on expressed RNA transcripts reveals functional non-coding mutations in melanoma.","description":"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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-03-10T23:13:53.688Z","creation":"2025-08-13T03:04:14.01Z"},"accession":"S-EPMC12256795","cross_references":{"pubmed":["40359938"],"doi":["10.1016/j.ajhg.2025.04.005"]}}