[Analyses of mutator gene mutations in familial gastric cancers]

The clinical and genetic studies have been very few on a familial predisposition to gastric cancers. We defined the criteria as familial gastric cancer (FGC) in which at least three relatives in two generations have gastric cancers, with one of the relatives having been diagnosed at less than 50 years of age. Other hereditary tumors, such as cancer family syndrome of hereditary nonpolyposis colorectal cancer(HNPCC), should be excluded. To clarify the carcinogenesis in FGC, we examined genetic alterations in six cancers from four FGC kindreds. Four (67%) cancers showed replication error, indicating that microsatellite instability is highly associated with not only HNPCC but also FGC. However, no germline mutation was found in the whole coding sequences of hMSH2 and hMTH1, or in the conservative regions of hMLH1 in any patients. Only few alterations were found at the small repeated sequences in the transforming growth factor-beta type II receptor gene in FGC tumor DNA. These results indicate that the carcinogenetic process of FGC may be different from that of HNPCC.