Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred.

A germ-line mutation of hMSH6 (also called GTBP) was found in a hereditary nonpolyposis colorectal cancer (HNPCC)-like patient in whom germ-line mutations of hMSH2, hMSH3, or hMLH1 had not been detected. The patient had rectal cancer and two colon adenomas at 62 years of age and a weak family history of gastrointestinal tumors, indicating atypical HNPCC. Somatic mutations of hMSH6 were observed in three colorectal tumors from the patient, indicating two-hit inactivation. Microsatellite instabilities at mononucleotide repeats were detected in all three tumors. These data suggest that hMSH6 is responsible for tumorigenesis in atypical HNPCC.