A T(3-8) CHROMOSOMAL TRANSLOCATION ASSOCIATED WITH HEPATITIS-B VIRUS INTEGRATION INVOLVES THE CARBOXYPEPTIDASE-N LOCUS

Integrated hepatitis B virus (HBV) DNA is found in the great majority of human hepatocellular carcinomas, suggesting that these viral integr ations may be implicated in liver ontogenesis. Besides the insertional mutagenesis characterized in a few selected cases and the contributio n of viral transactivators to cell transformation to malignancy, HBV h as been shown to generate gross chromosomal rearrangements potentially involved in carcinogenesis, Here, we report a t(3;8) chromosomal tran slocation present in a hepatocellular carcinoma developed in noncirrho tic liver tissue, One side of the translocation, in 8p23, is shown to he in the vicinity of the carboxypeptidase N gene, a locus that is hea vily transcribed in liver tissue and frequently deleted in hepatocellu lar carcinomas and other epithelial tumors. The other side of the tran slocation, in 3q27-29, is widely implicated in several types of transl ocations occurring in different malignancies, such as large cell lymph omas. The present data strongly support a model in which HBV-induced c hromosomal rearrangements play a key role during multistep liver oncog enesis.