[A novel genetic disorder of Lynch syndrome - EPCAM gene deletion]

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer, HNPCC, is a cancer-predisposing autosomal-dominant hereditary disorder caused by defects of the mismatch repair(MMR)system during DNA replication. Not only colorectal cancer, but malignancies in various organs, e.g., endometrium, stomach, small intestine, and urinary tract, occur in people of a relatively young age and accumulate in the family; therefore, this syndrome is considered to be a very important clinical entity with regard to the cancer treatment strategy. Germline mutations of 4 MMR genes, e.g., MLH1, MSH2, MSH6 and PMS2, had been identified as the cause of this disease, however, a novel mechanism, epigenetic inactivation of MSH2 gene due to hypermethylation of promotor region by the deletion of 3'part of epithelial cell adhesion molecule(EPCAM) gene which is located upstream of the MSH2 gene, has been reported in recent years. Therefore, it should be kept in mind in genetic testing and/or counseling for Lynch syndrome case with MSH2 defect that there might be a deletion of the EPCAM gene. In this review, the significance of the EPCAM gene defect in the management for Lynch syndrome is briefly introduced.