Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals.

ABSTRACT: The expression of eukaryotic genes relies on the precise 3'-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers - particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation - have received less attention. Here, we systematically analysed somatic mutations affecting 3'UTR polyadenylation signals in human cancers using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyaden

SUBMITTER: Kainov Y 

PROVIDER: S-EPMC11634062 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature