Chang M H, Chen P J, Chen J Y, Lai M Y, Hsu H C, Lian D C, Liu Y G, Chen D S
Department of Pediatrics, Pathology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Hepatology. 1991 Feb;13(2):316-20.
In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age. We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg. The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences. A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated. In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues. Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences. The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma. With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus.
在台湾，肝细胞癌是5至14岁儿童中的主要恶性肿瘤之一。我们研究了8名血清HBsAg和母亲HBsAg呈阳性的儿童的肝细胞癌组织和非肿瘤性肝组织中乙肝病毒DNA的状况。8名儿童中有5名的肝细胞癌组织显示乙肝病毒DNA整合到宿主细胞DNA序列中。在4名儿童中显示出单一位点整合模式，在1名儿童中显示出多位点整合模式。在其余3名儿童的肿瘤组织中未检测到乙肝病毒DNA。使用乙肝病毒基因组的亚基因组片段作为探针，我们发现X基因片段和表面抗原基因片段是最保守的序列。儿童肝细胞癌中乙肝病毒DNA的单一位点整合可能击中关键区域，导致插入诱变和肝细胞癌的早期发生。由于潜伏期短且早年接触环境致癌物较少，儿童肝细胞癌可能为研究乙肝病毒的致癌潜力提供一个良好的模型。
