Rearrangement of cellular DNA occurs in the vicinity of the woodchuck hepatitis virus integration region in hepatocellular carcinoma

Abstract

Insulin like growth factor II (IGF-II)is a highly mitogenic fetal growth factor suspected of regulating the paracine and, or the autocrine mode of action. A highsteady state level of IGF-II RNA was observed in three hepatocellular carcinomas (HCCs) from one wood\-chuck where uninfectedand infected normal liver RNA did not hyridize to IGF-II probe. The woodchuck hepatitis virus (WHV) integration patternin two of these tumors was identical, suggesting that they are metastasized. Unique flanking sequences from right and leftvirus-host junctions were determined in order to check whether the three viral integra\-tion in three different tumors arosefrom metastasis. Single copy of WHV genome was integrated in host chromosome of one tumor (tumor # 1) which had intact surface(S), core (C) and polymerase (P) sequences. Unique flanking sequences from the tumor 社 1 (￡coRI-HIII, 1.7 kb) were usedto map the sequences of the other two tumors. The mapping analyses revealed that all three tumors (contain different flankingsequences. These results could verify that, though three tumors^ show high level expression of IGF-II, they did not resultfrom metastasis. The mapping analyses also revealed that in tumor # 1 chromo\-somal rearrangement occurrs about 11 kb awayfrom the left side of integrated WHV and there was a gross rearrangement of host chromosome in the right side. These results confirmed that though three tumorsfrom one II expression, they are not from metastasis.