Lung M L, Chan W C, Zong Y S, Tang C M, Fok C L, Wong K T, Chan L K, Lau K W
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Cancer Epidemiol Biomarkers Prev. 1996 Apr;5(4):277-84.
A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in esophageal carcinomas in mainland China and Hong Kong was established. This study involved 209 squamous cell carcinoma specimens obtained from five different geographical locales in China: Zhengzhou, Taiyuan, Shantou, Guangzhou, and Hong Kong. Zhengzhou and Shantou were high-incidence regions for esophageal cancer, whereas the other three regions had low or intermediate incidence of the disease. Analysis by single-strand conformation polymorphism and DNA sequencing showed that 87 specimens (41.6%) contained mutations in exons 5-8 of the p53 gene compared to 163 cases (78%) that had accumulation or aberrant expression of the protein, as detected by immunohistochemical staining. Point mutations accounted for 80.4% (87/107) of all genetic changes. The specimens from northern China exhibited fewer p53 gene aberrations and a more even distribution of mutations in exons 5-8 compared to those from southern China in which 60% of all mutations were found in exon 5. A major hot spot was found at codon 176 in exon 5, where 41 samples from Shantou, Guangzhou, and Hong Kong had a G-->T transversion. It is likely that among southern Chinese this codon is susceptible to mutagenesis by carcinogens. Codons 175, 203, 245, 250, 273, and 282 were also shown to be mutational hot spots, with three or more mutations observed at each site. The p53 mutational data obtained in this study showed that Chinese esophageal carcinomas are often associated with some unique genetic alterations, which may be attributed to specific dietary or environmental carcinogens that affect the Chinese but not Caucasians.
建立了中国大陆和香港食管癌中p53肿瘤抑制基因第5至8外显子的突变谱。本研究涉及从中国五个不同地理区域获取的209例鳞状细胞癌标本，这些区域分别为郑州、太原、汕头、广州和香港。郑州和汕头是食管癌高发地区，而其他三个地区该病发病率较低或处于中等水平。通过单链构象多态性分析和DNA测序表明，与免疫组织化学染色检测到的163例（78%）蛋白质积累或异常表达的病例相比，87例标本（41.6%）在p53基因第5至8外显子中存在突变。点突变占所有基因变化的80.4%（87/107）。与中国南方的标本相比，中国北方的标本p53基因畸变较少，第5至8外显子中的突变分布更为均匀，在中国南方，所有突变的60%发生在第5外显子。在第5外显子的密码子176处发现了一个主要热点，来自汕头、广州和香港的41个样本在此处发生了G→T颠换。在中国南方人群中，这个密码子很可能易受致癌物诱变。密码子175、203、245、250、273和282也被证明是突变热点，每个位点观察到三个或更多突变。本研究获得的p53突变数据表明，中国食管癌常与一些独特的基因改变相关，这可能归因于影响中国人而非高加索人的特定饮食或环境致癌物。
