新疆南部地区维吾尔族妇女宫颈癌组织中人乳头状瘤病毒16型L1基因突变谱分析  

Mutations of human papillomavirus(HPV)16 type L1 genes from cervical carcinoma biopsies in southern Xinjiang Uygur women

作　　者：马正海[1] 张富春[1] 梅新娣[1] 马彩玲[2] 刘开江 

机构地区：[1]新疆大学生命科学与技术学院分子生物学重点实验室新疆生物资源基因工程重点实验室,乌鲁木齐830046 [2]新疆医科大学第一附属医院妇科 [3]新疆肿瘤医院妇科

出　　处：《中华医学杂志》2004年第12期987-991,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目 (3 9960 0 79) ;新疆维吾尔自治区自然科学基金资助项目(2 0 0 2 2 110 3 )

摘　　要：目的　探讨新疆南部地区维吾尔族妇女宫颈癌组织中人乳头状瘤病毒 16型L1基因的变异 ,并预测L1蛋白的功能变化。方法　从 19份中国新疆南部地区维吾尔族妇女宫颈癌活检组织标本中提取DNA ,以此DNA为模板 ,PCR扩增HPV16L1全长基因 ,PCR产物直接测序或克隆后测序 ,分析新疆维吾尔族妇女宫颈癌组织HPV16L1基因多态性及HPV16L1蛋白功能的变化。结果PCR检测结果显示宫颈癌组织中HPV16L1阳性率为 84 2 1% (16 / 19) ;测序和序列分析表明L1基因核苷酸多处发生变异 ,并引起编码氨基酸的变异 ,L1基因在核苷酸水平形成上 6种突变模式(XJL1 1～XJL1 6 ) ,各模式与HPV16原型比较 ,同源性在 99 6 9%～ 99 87%之间。XJL1 1发生的 4处变异是所有变异序列所共有的 ,XJL1 2～XJL1 6在XJL1 1变异的基础上增加了不同的变异 ;在氨基酸水平上形成 4种突变模式 ,其中XJL1 1/ 2 / 3突变模式占 76 92 % (8/ 13) ,是突变的主流模式 ;以上突变引起HPV16L1蛋白疏水性和抗原性的改变 ,继而改变了L1蛋白的结构及功能。结论　中国新疆南部地区维吾尔族妇女宫颈癌患者组织中HPV16L1基因发生多位点变异 ,并形成多种突变模式和突变的主流模式 ;这些突变引起HPV16L1蛋白疏水性和抗原性的改变 。ObjectiveTo study the mutations of Human Papillomavirus (HPV)16 type L1 genes of cervical carcinoma biopsies from Uygur women in Southern Xinjiang,and analyze changes of L1 protein function.MethodsThe tissue DNA was extracted from cervical carcinoma biopsies. HPV16 L1 genes were amplified by PCR from the DNA HPV16 type L1 genes were sequenced and analyzed.ResultsThe result of PCR showed that the positive rate of HPV16 L1 was 84.21%(16/19). These DNA were sequenced,and we found some mutations in comparison with the previously published sequence of prototype HPV16 L1. Some of the mutations changed the triplet codes,subsequently led to changes of amino acids. The mutations of all thirteen HPV16 L1 fragments formed six patterns(XJL1-1～XJL1-6) at nucleic acid level. Compare to HPV16 prototype,their homology were 99.69% to 99.87%. There were four mutations in nucleic acid sequences of XJL1-1,which occurred also in XJL1-2～XJL1-6. Moreover,there are other mutations in XJL1-2～XJL1-6 besides the four mutations in XJ L1-1. The mutations of all thirteen HPV16 L1 fragments formed four patterns at amino acid level,among the mutations XJL1-1/2/3 was by 76.92% (8/13). ConclusionHPV16 type L1 genes from cervical carcinoma biopsies occurred some mutations in Uygur women from southern Xinjiang,and formed several patterns as well as mainstream pattern. The mutations of L1 proteins changed its hydrophobicity and antigenicity. The research suggested that the mutations of HPV16 type L1 genes associated with HPV16 phylogenesis and escape from immune recognition.

关 键 词：新疆南部地区 维吾尔族 妇女 宫颈癌 癌组织 人乳头状瘤病毒16型 L1基因突变谱 宫颈肿瘤 

分 类 号：R737.33[医药卫生—肿瘤]