Three novel germline mutations in MLH1 and MSH2 in families with Lynch syndrome living on Jeju island, Korea

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (

Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study

“…Of note, we discovered a valine‐to‐aspartate (V384D) substitution in MLH1 in 8 of 365 (2%) patients. This variant was previously described to be a possible germline susceptibility polymorphism in East Asian populations, and reportedly increases carriers’ risks for hereditary nonpolyposis colorectal and gastrointestinal cancers . Our group had also previously reported the recurrence of this polymorphism in unrelated Chinese patients who had Lynch syndrome and at least two or more family members who had early‐onset colorectal cancer or Lynch syndrome‐associated cancers .…”