Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: Their relationship to clinicopathological features

To elucidate cytogenetic alterations underlying human hepatocellular carcin omas (HCCs), we used a comparative genomic hybridization (CGH) method to an alyze 41 cases of hepatocellular carcinoma (HCC) including 15 well differen tiated HCCs, 14 moderately differentiated HCCs, and 12 poorly differentiate d HCCs. Of these, 27 patients were chronically infected with hepatitis C vi rus (HCV), and the remaining patients were positive for hepatitis B virus ( HBV). The most common sites of increase in DNA copy number were 1q (78% of the cases) and 8q (66%) with minimal overlapping regions at 1q24-25 and 8q2 4, respectively. Frequent decreases in copy number were observed at 17p (51 %), 16q (46%), 13q13-14 (37%), 4q13-22 (32%), 8p (29%), and 10q (17%). In 6 cases (15%), an amplification was found in the region of 11q13. A gain of 8q24 was significantly associated with well-differentiated HCCs (P<.05), wh ereas a loss of 13q13-14 and amplification of 11q13 were Linked to moderate ly and poorly differentiated HCCs (P<.01). These observations suggest that a gain of 8q24 is an early event and that a loss of 13q13-14 and amplificat ion of 11q13 are a late event in the course of Liver carcinogenesis. A gain of 10q (7/41) was detected exclusively in cases with HCV infection. In con trast, an amplification of 11q13 was preferentially found in HBV-positive H CCs. These findings raise the hypothesis that, although many generic altera tions are basically common to both HCV-positive and HBV-positive turners, t he process of carcinogenesis may be to some extent different between these two types of rumors.