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中国四川宫颈癌患者中HPV16分离株的HPV流行率、E6序列变异及物理状态

HPV prevalence, E6 sequence variation and physical state of HPV16 isolates from patients with cervical cancer in Sichuan, China.

作者信息

Qiu Ai-Dong, Wu En-Qi, Yu Xiang-Hui, Jiang Chun-Lai, Jin Ying-Hua, Wu Yong-Ge, Chen Yue, Chen Yan, Shan Ya-Ming, Zhang Guo-Nan, Fan Ying, Zha Xiao, Kong Wei

机构信息

College of Life Science, Vaccines Research Center, Jilin University, Changchun 130012, China.

出版信息

Gynecol Oncol. 2007 Jan;104(1):77-85. doi: 10.1016/j.ygyno.2006.07.016. Epub 2006 Sep 12.

Abstract

OBJECTIVES

Infection with high-risk human papillomavirus (hr-HPV) is an important factor associated with cervical cancer. The genetic mutation of HPV16 E6 and integration of HPV16 DNA in the cervical carcinoma tissues are considered important genetic changes in cervical lesion progression. But the studies of hr-HPV epidemiology are relatively less in the area of Sichuan, China. Therefore, we investigated the prevalence of 9 high-risk subtypes and analyzed the genetic mutation characteristic of HPV16 E6 and physical state of HPV16 DNA.

METHODS

The fragments of L1 and E6 genes were amplified by PCR or nested PCR and then directly sequenced. Further, the multiplex PCR for HPV16 E2 and E6 genes was performed for detection of integration.

RESULTS

HPV16, 58 and 18 were prominent, accounting for 78.6%, 20.0% and 9.7%, respectively in 145 isolates. E6 variants revealed that the European (EP) prototype and East Asia (EA) strain were 26 (23.0%) and 34 (30.1%), respectively. Furthermore, there were 14 base substitutions in E6 regions of the study group, of which 12 resulted in amino acid changes and the rest was silent mutation. Significantly, the 240G substitution exactly located the P53 degradation site. Overall, 8 of 114 (7.0%) isolates only contained integrated HPV16 DNA, 43 (37.7%) only contained episomal DNA and 63 (55.3%) contained both integrated and episomal DNA. The proportion of disruption of an intact E2 gene in the patients with cervical cancer is much lower than that in the previous studies.

CONCLUSIONS

HPV16, 58 and 18 were mainly prevailing subtypes in patients with cervical cancer from Sichuan areas, China and EP/EA strains were predominant in these areas. Some mutations of E6 gene, which lead to the amino acid changes, may be more potentially carcinogenic and the proportion of disruption of an intact E2 gene is much lower.

摘要

目的

高危型人乳头瘤病毒(hr-HPV)感染是宫颈癌发生的重要相关因素。宫颈癌组织中HPV16 E6基因突变及HPV16 DNA整合被认为是宫颈病变进展过程中的重要遗传学改变。但在中国四川地区,hr-HPV流行病学研究相对较少。因此,我们调查了9种高危亚型的流行情况,并分析了HPV16 E6基因突变特征及HPV16 DNA的物理状态。

方法

采用PCR或巢式PCR扩增L1和E6基因片段,然后直接测序。此外,进行HPV16 E2和E6基因的多重PCR检测整合情况。

结果

在145株分离株中,HPV16、58和18型最为突出,分别占78.6%、20.0%和9.

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