云南HPV-16型E6、E7基因的突变分析

人乳头瘤病毒(Human papillomavirus,HPV)16型(HPV-16)是引起宫颈癌的一种主要高危型病毒,其2个致癌基因E6和E7的核酸序列变异可能会影响其对宿主细胞的致癌性,已有研究表明其序列突变呈现地域差异性。因此,研究不同地域HPV-16这2个基因的变化情况是宫颈癌流行病学调研的主要内容,也可为研究E6和E7的致癌性积累数据。研究以NCBI登录号为NC_001526.2的HPV-16型病毒的序列为参照,采用Neighbor-joining方法对云南地区74例HPV-16样本的E6、E7的DNA序列构建进化树,结果显示:只有亚洲和欧洲变异亚型,而没有发现非洲1、非洲2、亚-美洲和北美洲这4种变异亚型。DNA序列分析显示:E6的碱基突变以T178G(D25E,59.46%)和T350G(L83V,8.11%)为主,E7的碱基突变主要以A647G(N29S,59.46%)和T846C(同义突变,60.81%)为主。发现E6的新突变有A95G(同义突变,1.35%)和A135G(K11R,1.35%);E7的新突变有C625T(L22F,1.35%)、C627T(同义突变,12.16%)、G689A(G43E,1.35%)、T748G(S63A,1.35%)。此外还发现有一个共突变现象:T178G(D25E,59.46%)-A647G(N29S,59.46%)-T843C(同义突变,21.62%)-T846C(同义突变,60.81%)。

Mutational Analysis of HPV16 Type E6, E7 Genes in Yunnan Province

Human papillomavirus type 16（HPV-16） is a high-risk major virus causing cervical cancer.Nucleic acid sequence variations of its oncogene E6 and E7 may have affected its host cells＇ carcinogenesis,and it had been studied that its variation assumes areal differences.Therefore,survey and analysis of the variations of these two oncogenic genes in different region is a main content of epidemiology of cervical cancer,and it can amass data associated the oncogenesis of E6 and E7.The DNA sequences of E6 and E7 genes of 74 cases of human papillomavirus 16 type（HPV-16） cases in Yunnan province were used to construct a phylogenetic tree respectively by using the Neighbor-joining method and the reference sequence of HPV-16（NCBI accession num-ber：NC_001526.2）.The results showed that only Asian and European variant subtypes exist,but not any African type 1,African type 2,Asian-American and North-American variants were found.DNA sequence analysis showed that base mutation of E6 mainly was T178G（D25E,59.46%） and T350G（L83V,8.11%）,while E7 genes mainly was A647G（N29S,59.46%） and T846C（synonymous mutation,60.81%）.It was found that new mutations of E6 was A95G（synonymous mutation,1.35%）and A135G（K11R,1.35%）,new mutations of E7 mutations was C625T（L22F,1.35%）,C627T（synonymous mutation,12.16%）,G689A（G43E,1.35%） and T748G（S63A,1.35%）.In addition,a co-mutational phenomenon was also found：T178G（D25E,59.46%）-A647G（N29S,59.46%）-T843C（synonymous mutation,21.62%）-T846C（synonymous mutation,60.81%）.