MUTATIONS OF 2 PMS HOMOLOGS IN HEREDITARY NONPOLYPOSIS COLON-CANCER

HEREDITARY nonpolyposis colorectal cancer (HNPCC) is one of man's comm onest hereditary diseases(1). Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease(2-8). In p articular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch re pair genes mutS and mutL, respectively, were shown to be mutated in a subset of HNPCC cases(9-16). Here we report the nucleotide sequence, c hromosome localization and mutational analysis of hPMS1 and hPMS2, two additional homologues of the prokaryotic mutL gene. Both hPMS1 and hP MS2 were found to be mutated in the germline of HNPCC patients. This d oubles the number of genes implicated in HNPCC and may help explain th e relatively high incidence of this disease.