Somatic CpG hypermutation is associated with mismatch repair deficiency in cancer

ABSTRACT: Somatic hypermutation in cancer has gained momentum with the increased use of tumour mutation burden as a biomarker for immune checkpoint inhibitors. Spontaneous deamination of 5-methylcytosines to thymines at CpG dinucleotides is one of the most ubiquitous endogenous mutational processes in normal and cancer cells. Here, we performed a systematic investigation of somatic CpG hypermutations at a pan-cancer level. We studied 30,191 cancer patients and 103 cancer types and developed an algorithm to classify somatic CpG hypermutation. Across cancer types, we observed the highest prevalence in paediatric leukaemia (3.5%), paediatric high-grade glioma (1.7%), and colorectal cancer (1%). We discovered germline and somatic mutations in the mismatch repair complex MutSα (MSH2-MSH6) as genetic driv

SUBMITTER: Prof Joachim Weischenfeldt 

PROVIDER: S-SCDT-10_1038-S44320-024-00054-5 | biostudies-other |

REPOSITORIES: biostudies-other