DGGE SCREENING OF MUTATIONS IN MISMATCH REPAIR GENES (HMSH2 AND HMLH1) IN 34 SWEDISH FAMILIES WITH COLORECTAL-CANCER

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dom inantly inherited syndrome which confers an increased risk for colorec tal cancer and endometrial cancer as well as other tumors. It is cause d by germline DNA mismatch repair (MMR) gene mutations in five MMR gen es, hMSH2, hMLH1, hPMS1, hPMS2 and hMSH6. Finding mutations in these h igh risk families means that you can offer presymptomatic carrier diag nosis and thereby identify individuals with a very high risk for cance r. These persons benefit from counseling and should be offered surveil lance. We have used DGGE to screen members from 34 families for mutati ons in hMLH1 and hMSH2. Six mutations in five families were found, fiv e of these mutations are new. Besides, three new polymorphisms were id entified. The mutations were found in two of seven Amsterdam criteria HNPCC families and in three of four families with at least one case of early onset of CRC (before 35), suggesting there are appropriate fami lies to be chosen for mutation screening in MMR genes.