EVIDENCE FOR THE PRESENCE OF 2 TUMOR-SUPPRESSOR GENES FOR HEPATOCELLULAR-CARCINOMA ON CHROMOSOME 13Q

The concept that genetic changes accumulate during development and progression of cancer is widely accepted. Frequent allelic losses at chromosome 13q have been found in hepatocellular carcinomas (HCCs), and a known tumour-suppressor at 13q14, the retinoblastoma (RE) gene, is thought to be the target of those events. However, no strong evidence has emerged to support a significant role of RE during hepatocarcinogenesis. To investigate the minimal area(s) of loss on chromosome 13q in HCCs, we analysed DNAs isolated from 92 tumours for loss of heterozygosity (LOH) at 13 loci on chromosome 13q, using polymorphic microsatellite markers. In 30 (32.6%) of 92 cases we detected LOH for at least one locus on chromosome 13q and 20 revealed a partial or interstitial deletion of chromosome 13q. Deletion mapping of these 20 tumours indicated two separate commonly deleted regions: one was located in the region including RE and the other was located in the region including the BRCA2 locus. These findings suggest that at least one putative tumour-suppressor gene for HCC other than RE, possibly BRCA2, exists on chromosome 13q.