The novel germline mutation of hMSH2 gene in a case of a hereditary non-polyposis colorectal cancer (HNPCC) patient who meets the revised Amsterdam criteria.

Hereditary non-polyposis colorectal cancer (HNPCC) is a very important clinical entity in oncology. In order to identify HNPCC, the international diagnostic criteria named "Amsterdam criteria" have been used. In this report, we present a case of an HNPCC patient who met the revised Amsterdam criteria after the sequential history taking in which a novel germline mutation of hMSH2 gene was detected by genetic testing. The proband was a 69-year-old Japanese female who was admitted to our hospital with a diagnosis of advanced ascending colon cancer. Microsatellite instability (MSI) analysis revealed high MSI in the resected tumor tissue. PCR/direct sequencing analysis of the genomic DNA revealed the TTG(Leu) to TAG(Stop) nonsense mutation at codon 302 in exon 5 of the hMSH2 gene, which was considered to be a pathogenic mutation. According to the Human Mutation Database and International Collaborative Group on HNPCC (ICG-HNPCC) Database, this type of nonsense mutation is the first report in the hMSH2 gene.