Case Report and Literature Review: Diagnosis, Tailored Genetic Counseling and Cancer Prevention for a Locally Advanced dMMR/MSI-H/TMB-H Lung Cancer Patient With Concurrent Lynch Syndrome Mediated by a Rare PMS2 Splicing Variant (c.1144+1G>A).

ABSTRACT: Lynch syndrome (LS) is a cancer-predisposing genetic disease mediated by pathogenic mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. Accumulating evidence demonstrates that there is significant biological heterogeneity across MMR genes. Compared to MLH1 and MSH2, PMS2 variant carriers have a much lower risk for LS-related cancers. Tumors in MLH1 and MSH2 variant carriers often display MMR deficiency (dMMR) and/or high microsatellite instability (MSI-H), two predictive biomarkers for immunotherapy efficacy. However, tumors in PMS2 variant carriers are largely microsatellite stable (MSS) instead of MSI. Therefore, the optimal management of cancer patients with LS requires the integration of disease

SUBMITTER: Han Q 

PROVIDER: S-EPMC8804326 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature