A t(3;8) chromosomal translocation associated with hepatitis B virus intergration 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 integrations may be implicated in liver oncogenesis. Besides the insertional mutagenesis characterized in a few selected cases and the contribution of viral transactivators to cell transformation to malignancy, HBV has been shown to generate gross chromosomal rearrangements potentially involved in carcinogenesis. Here, we report a t(3;8) chromosomal translocation present in a hepatocellular carcinoma developed in noncirrhotic liver tissue. One side of the translocation, in 8p23, is shown to be in the vicinity of the carboxypeptidase N gene, a locus that is heavily transcribed in liver tissue and frequently deleted in hepatocellular carcinomas and other epithelial tumors. The other side of the translocation, in 3q27-29, is widely implicated in several types of translocations occurring in different malignancies, such as large-cell lymphomas. The present data strongly support a model in which HBV-induced chromosomal rearrangements play a key role during multistep liver oncogenesis.
Pineau
P
P
Unité de Recombinaison et Expression Génétique, Institut National dela Santé et de la Recherche Médicale (INSERM) U163, Institut Pasteur,Paris, France.
Marchio
A
A
Terris
B
B
Mattei
M G
MG
Tu
Z X
ZX
Tiollais
P
P
Dejean
A
A
D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D001121:Lysine Carboxypeptidase / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014178:Translocation, Genetic; D016662:Virus Integration
D001121:Lysine Carboxypeptidase