NOVEL GERMLINE MUTATIONS OF HMSH2 IN A PATIENT WITH HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (HNPCC) AND IN A PATIENT WITH 6 PRIMARY CANCERS

We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis col orectal cancer (HNPCC) and in a patient with multiple primary cancers. Screening the entire coding regions of both genes using polymerase ch ain reaction-single strand conformation polymorphism (PCR-SSCP) analys is, we found two novel germline mutations in hMSH2. One was a l-bp ins ertion in exon 12, detected in a patient who had undergone surgery six times for independent tumors (four primary colorectal carcinomas, a s mall intestinal carcinoma, and an endometrial cancer). The other, in a second patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that resulted in substitution of phenylalanine for leucine. This conservative alteration was not found in any of 50 normal control s, but we cannot exclude the possibility that it may represent a rare polymorphism rather than a factor in the disease.