中国湖北地区HPV16型E6和E7基因变异和进化发生学研究  

The Study of Gene Variation and Phylogenetic Analysis of HPV16 E6 and E7 Gene in Hubei,China

作　　者：丁晓华[1] 张帆[2] 蔡红斌[2] 杨占秋[1] 

机构地区：[1]武汉大学医学院医学病毒研究所,武汉430071 [2]武汉大学中南医院妇瘤科,武汉430071

出　　处：《病毒学报》2010年第5期368-372,共5页Chinese Journal of Virology

摘　　要：研究中国湖北地区宫颈癌患者的人乳头瘤病毒16型E6和E7的变异以及HPV16变异体的分布。从宫颈癌患者手术切除标本提取组织DNA,用HPV16 E6和E7特异性引物进行PCR扩增,对扩增的部分E6和E7产物片段进行测序分析。在80例宫颈癌组织DNA中有41例发生E6基因178位核苷酸的突变,突变频率58.75%,相应核苷酸改变为Asp-Glu,E7 647在31例测序样品中有22例发生核苷酸序列A到G改变,使29位氨基酸由Asn变为Ser,突变频率70.97%,结果显示在E6和E7基因的178位和647位核苷酸存在高频率的碱基变异。对E6和E7基因的进化树分析表明,中国湖北地区流行的HPV16病毒株主要为亚洲型变异体(As),其次为欧洲型(E),没有发现非洲-1型(Af-1),非洲-2型(Af-2)和亚洲美洲型(AA)HPV16变异体,中国湖北地区流行的As变异体是否有更高的致宫颈癌的风险还有待于进一步对不同阶段CIN和正常宫颈上皮样品的E6和E7基因进行序列分析和对变异体蛋白进行功能研究。To study the gene variation and the distribution of HPV16 variant in Hubei,China,DNA was extracted from cervical cancer tissue samples.The E6 and E7 genes of HPV16 were amplified and the PCR products were sequenced using E6-and E7-specific primers.Fortyseven cases were found mutations at nucleotide position 178 of HPV16 E6 gene in 80 cervical cancer samples.This mutation resulted in amino acid change from Asp to Glu.The rate of mutation at nucleotide position 178 of E6 gene was 58.75%.Twenty two cases were found mutations at nucleotide position 647 of HPV16 E7 gene in 31 cervical cancer samples.This mutation resulted in amino acid change from Asn to Ser.The rate of mutation was 70.97%.These results showed that mutations at nucleotide position 178 of E6 gene,nucleotide position 647 of E7 gene of HPV16 in cerveical cancer samples were prevalent in Hubei,China.Phylogenetic analysis showed that Asian（As） variants of HPV16 are predominated in Hubei,China.European（Ep） varinats were also found in Samples in Hubei areas.None of Asian American（AA）,African-1（Af-1）,African-2（Af-2） variants of HPV16 was found in this region.Whether Asian（As） variants of HPV16 are more oncogenic and play a much more important role in the progress of cervical cancer than European（Ep） variants is not clear.More sequences of E6 and E7 gene in CIN and normal cervical tissue samples and study of the function of E6 and E7 protein of these HPV16 variants are needed to adress above question.

关 键 词：人宫颈癌 人乳头瘤病毒16型 序列分析 突变 

分 类 号：R373.9[医药卫生—病原生物学]