Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with constitutional mismatch repair deficiency.

ABSTRACT: Constitutional mismatch repair deficiency (CMMRD), caused by bi-allelic germline variants in mismatch repair (MMR) genes, is associated with high cancer incidence early in life. A better understanding of mutational processes driving sequential CMMRD tumors can advance optimal treatment. Here, we describe a genomic characterization on a representative collection of CMMRD-associated tumors consisting of 41 tumors from 17 individuals. Mutational patterns in these tumors appear to be influenced by multiple factors, including the affected MMR gene and tumor type. Somatic polymerase proofreading mutations, commonly present in brain tumors, are also found in a T-cell lymphoblastic lymphoma displaying associated mutational patterns. We show prominent mutational patterns in two second primary hemat

SUBMITTER: Weijers DD 

PROVIDER: S-EPMC12078508 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature