MUTATIONS IN MLH1 ARE MORE FREQUENT THAN IN MSH2 IN SPORADIC COLORECTAL CANCERS WITH MICROSATELLITE INSTABILITY

The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequen ce of defective DNA mismatch repair. Mutations in the DNA mismatch rep air genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. M icrosatellite instability is also seen in 10-16% of sporadic colorecta l cancers. A limited number of MSH2 and MLH1 mutations have been descr ibed for sporadic colorectal cancers. In this study, we screened 12 pr imary sporadic colorectal cancers with microsatellite instability for mutations in MSH2 and MLH1 by using reverse transcription-polymerase c hain reaction (RT-PCR) and single-strand-conformation-variant (SSCV) a nalysis. Eight mutations were identified in six tumors. One mutation i n MLH1 was found to be present in the patient's germline DNA, Four tum ors had somatic mutations in MLH1, and, in two of these tumors, two di fferent mutations were identified, A single tumor had a somatic MSH2 m utation. Our observations suggest that MLH1 is mutated more frequently than MSH2 in sporadic colorectal cancers with microsatellite instabil ity. (C) 1997 Wiley-Liss, Inc.