Ng I O, Srivastava G, Chung L P, Tsang S W, Ng M M
Department of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam.
Cancer. 1994 Jul 1;74(1):30-7. doi: 10.1002/1097-0142(19940701)74:1<30::aid-cncr2820740107>3.0.co;2-4.
Gene deletion, point mutations, and abnormalities in expression of the tumor suppressor gene p53 in hepatocellular carcinoma have been reported to occur with varying frequency in different geographic regions.
To assess the expression and point mutation of the p53 gene, 31 patients with hepatocellular carcinomas were examined using Northern blotting, immunohistochemical methods, and DNA sequencing. All patients were Chinese, and 90.3% were positive for hepatitis B surface antigen (HBsAg).
p53 transcript or protein was found in 14 (48.4%) of the 31 patients. Detectable p53 mRNA transcripts were found in 10 patients, and p53 protein was detected in 8 patients. In most cases of patients who had detectable p53 mRNA transcripts, the transcripts in the tumors were exhibited at a higher level than they were in the corresponding nontumorous livers. No p53 protein was detected in the nontumorous livers in all 31 patients. Six (23.1%) of the 26 tumors sequenced showed point mutation scattered in exons 5-9. Of these, only two were at codon-249, and the nature of these two mutations was G-to-T transversions. All but one of the six patients with point mutations had overexpression of the gene.
Our results show that scattered point mutations are not uncommon in hepatocellular carcinomas in patients from Hong Kong. The distribution pattern of the mutations seems to have no particular correlation with HBsAg status despite a high prevalence rate of HBsAg positivity in our patients. Consistent with a low aflatoxin exposure, aflatoxin-related specific mutation at codon-249 is much less related to the pathogenesis of hepatocellular carcinoma in Hong Kong Chinese people than in other regions with a high-aflatoxin exposure.
据报道，在不同地理区域，肝细胞癌中肿瘤抑制基因p53的基因缺失、点突变及表达异常的发生频率各不相同。
为评估p53基因的表达及点突变情况，采用Northern印迹法、免疫组化法及DNA测序对31例肝细胞癌患者进行检测。所有患者均为中国人，90.3%的患者乙肝表面抗原（HBsAg）呈阳性。
31例患者中有14例（48.4%）检测到p53转录本或蛋白。10例患者检测到可检测到的p53 mRNA转录本，8例患者检测到p53蛋白。在大多数检测到p53 mRNA转录本的患者中，肿瘤中的转录本水平高于相应的非肿瘤肝脏。31例患者的非肿瘤肝脏中均未检测到p53蛋白。在测序的26个肿瘤中，有6个（23.1%）显示点突变，分布在外显子5-9中。其中，只有两个位于密码子249，这两个突变的性质是G到T的颠换。6例有基因突变的患者中，除1例之外，其余患者的基因均有过表达。
我们的结果表明，香港患者的肝细胞癌中散在点突变并不少见。尽管我们的患者中HBsAg阳性率很高，但突变的分布模式似乎与HBsAg状态没有特别的相关性。与低黄曲霉毒素暴露一致，与黄曲霉毒素相关的密码子249特异性突变与香港中国人肝细胞癌发病机制的相关性远低于其他黄曲霉毒素高暴露地区。
