A Case of Hereditary Nonpolyposis Colorectal Cancer with Novel Germline Mutation of hMLH1

Abstract

Human homologues of the bacterial DNA mismatch repair genes, hMLH1 and hMSH2, assigned on chromosome 3p21-23 and 2p21-22 are involved in hereditary nonpolyposis colorectal cancer （HNPCC）. HNPCC is most frequently caused by germline mutations in the DNA mismatch repair gene hMLH1 or hMSH2. Loss of the wild-type allele results in a mutator phenotype and accelerating tumorigenesis, which especially cause carcinomas in the gastrointestional and genitourinary tracts. We examined germline mutations of mismatch repair genes, hMLH1 and hMSH2., in a patient with multiple primary neoplasms （multiple stomach cancer, colon cancer and brain tumor）. In screening by long RT-PCR from the RNA, we found skipping of exon 2 in hMLH1. The analysis of the genomic DNA showed a GT delation in the splice-donor site of exon 2, which is compatible with the splicing variant detected by long RT-PCR analysis. This is a novel germline mutation that has not been reported previously. We attempted to define the syndrome as a part of HNPCC.