Shafritz D A, Shouval D, Sherman H I, Hadziyannis S J, Kew M C
N Engl J Med. 1981 Oct 29;305(18):1067-73. doi: 10.1056/NEJM198110293051807.
We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm.
我们运用重组DNA技术和凝胶电泳，在肝细胞癌和慢性肝病患者的肝脏及肿瘤组织中查找乙型肝炎病毒DNA（HBV - DNA），并研究HBV - DNA整合入这些组织细胞基因组的情况。在血清中含有乙型肝炎表面抗原（HBsAg）的12例肝细胞癌患者的肿瘤中，检测到了整合的HBV - DNA；在8例HBsAg血清学阴性但抗 - HBsAg阳性患者的肿瘤中，也有3例检测到了整合的HBV - DNA。在某些情况下，整合的HBV - DNA也存在于非肿瘤性肝组织中，其杂交模式与肿瘤组织相同或不同。在5例HBsAg携带者中，他们有携带者状态的证据且患慢性肝病不到两年，肝脏组织中存在HBV - DNA但未发生整合。在2例携带HBsAg超过8年的患者中，HBV - DNA已整合入宿主基因组。这些数据表明，HBV - DNA整合入肝细胞发生在持续性HBV感染过程中，且先于明显肿瘤的发生。
