宫颈癌组织中HPV16型E6/E7序列突变分析

Mutations in the E6/E7 genes of human papillomavirus type 16 from cervical cancer tissue

目的分析泉州地区宫颈癌患者HPV16型E6/E7序列突变情况,探讨其与宫颈癌发生的相关性。方法取35例HPV16阳性的宫颈癌组织标本,采用PCR法扩增E6、E7全长基因。PCR产物直接测序,并与野生型序列进行比对。分析E6、E7基因的变异情况。结果 E6、E7基因的突变率分别为91.4%和89.2%。E6基因中有10个位点为错义突变,2个位点为无义突变。氨基酸突变频率最高的是D25E(77.1%)。E7基因中共发现5个突变位点,有2个位点为错义突变,3个位点为无义突变,突变频率最高是N29S和无义突变T846C(均为75.0%)。结论 HPV16E6、E7基因中最常见突变位点D25E、N29S和T846C可能与宫颈癌的发生密切相关,可为研究针对中国人群的HPV疫苗提供一定的线索。

To investigate mutations in E6/E7 genes of human papillomavirus type 16（HPV16） in patients with cervical cancer in Quanzhou area and explore the potential association between the mutations and cervical cancer,35 cervical cancer tissue with HPV 16 positive were collected in this study.DNA samples were amplified by polymerase chain reation（PCR）,then the products were directly sequenced and the results were compared with the prototype sequence.It was found that the prevalences of HPV 16 E6 and E7 variants were 91.4% and 89.2% respectively.Ten mis-sense variantions and 2 silent variantions were identified in E6.The hot spot of E6 nucleotide mutation was D25E,with a frequency of 77.1%.A total of 5 mutation spots was found in E7,including 2 mis-sense and 3 silent variations.Both N29S and T846C were the most common mutations,with the same ratio of 75.0%.It is suggested that the mutation of D25E,N29S and T846C are likely to be associated with ontogenesis of cervical cancer.This founding might provide valuable information for HPV vaccine development in China.