A NOVEL MISSENSE MUTATION IN THE DNA MISMATCH REPAIR GENE HMLH1 PRESENT AMONG EAST ASIANS BUT NOT AMONG EUROPEANS

In a search for germline mutations in the DNA mismatch repair genes hM SH2 and hMLH1 in Chinese patients with colorectal cancer we identified a novel missense mutation (V384D) in exon 12 of the hMLH1 gene in 4 o ut of 26 individuals. This mutation had not been observed in any of 10 9 German patients who either fulfill the clinical criteria of heredita ry nonpolyposis colorectal cancer or had developed colorectal cancer a t an early age. In a second series of experiments, DNA samples of 80 h ealthy Japanese and 100 healthy Germans were examined for the presence of the V384D mutation. It was observed in 4 Japanese, but in none of the German individuals. Thus, the V384D mutation seems to be confined to the East-Asian population. Since this missense mutation occurs at a less conserved region of the hMLH1 gene, it may represent a nonfuncti onal polymorphism. However, a role in the pathogenesis of colorectal c ancer cannot be ruled out from the present study.