Identification of minimal region of deletion on 8p23.1-22 associated with metastasis of hepatocellular carcinoma Free

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Loss of heterozygosity (LOH) at 8p is the most frequent chromosomal alteration in various types of human cancers including hepatocellular carcinoma (HCC). This suggests that one or more tumor suppressor genes (TSGs) may lie within the 8p. To further identify the precise location of the putative TSGs that might potentially be involved in the metastasis of HCC, we used 16 informative microsatellite markers in Japanese patients, which were selected from 61 published microsatellite markers, at 8p23.2, 8p23.1, 8p22, and 8p21 to compare the frequency of LOH in primary and metastatic cancer lesions of HCC by PCR-based analysis. A total of 62 informative cancer lesions (26 primary lesions, 36 metastatic lesions) from 22 informative cases of HCC were used in this study. The frequency of LOH at 8p23.2-21 with at least one marker was 19% (5 of 26) and 69% (25 of 36) in the informative primary lesions and metastastic lesions, respectively. Allelic loss at 8p23.2-21 was significantly more frequent in the metastatic cancer lesions than in the primary cancer lesions (P = 0.0001). More specifically, the frequency of LOH at D8S262 (8p23.2), D8S1819, D8S503, D8S1130, D8S552, D8S1109, (8p23.1), and D8S258 (8p22) was 50%, 60%, 36%, 46%, 60%, 50%, and 53%, respectively, in the metastatic cancer lesions. In contrast, allelic loss at the same markers was only detected in 14%, 17%, 8%, 9%, 0%, 14%, and 17%, respectively, in the primary lesions. These losses occurred more frequently in the metastatic lesions but not in primary lesions of the same HCC, suggesting that LOH at 8p23.2-22 regions may be involved in enhancing tumor aggressiveness, especially in the metastasis of tumors. Inactivation of unidentified TSGs within this region may contribute to the progression of HCCs. Our results suggest that the critical genes may lie at the restricted minimal regions of 8p23.2-22.