The novel germline mutation of hMSH2 gene in a case of a colon cancer patient without family history.

Hereditary non-polyposis colorectal cancer (HNPCC) is generally found from the patient's family history. The functional disorder of mismatch repair genes has been reported to be responsible for HNPCC. The proband was a 28-year-old Japanese female who was admitted to our hospital with a diagnosis of descending colon cancer. Although there was no previous or family history of malignant disorders within the first- and second-degree relatives, the early onset of colon cancer prompted genetic analysis with suspicion of HNPCC. PCR analysis of the primary tumor showed DNA replication errors at the six microsatellite regions. PCR/direct sequential analysis of the peripheral lymphocytes revealed a germline frameshift mutation due to deletion of TTCAA at nt. position from 650 to 654 in exon 4 of the hMSH2 gene. According to the Human Mutation Database and International Collaborative Group on HNPCC Database, this type of the frameshift mutation is the first report in the hMSH2 gene.