染色体外游离态的子宫颈癌HPV16分离株E1/E2区的基因序列重排

Presence of genetic rearrangements in E1/E2 regions of episomal HPV 16 isolates from cervical carcinomas

目的 观测子宫颈癌组织中呈染色体外质粒状态的HPV 16分离株E1/E2基因序列。方法 Southern转印杂交检测癌组织中HPV 16基因组的物理状态 ,对 8例游离状态的HPV 16分离株E1/E2区进行PCR扩增 ,克隆后酶切分析和DNA序列分析。结果 对 2 8例HPV 16阳性子宫颈癌中病毒DNA杂交结果显示 8例呈染色体外质粒方式存在。PCR克隆鉴定发现 8例分离株都具有完整的E1/E2区域。此外 4例分离株还带有不同比率的基因重排 ,序列检测证实E1/E2区存在有不同的重复序列插入、缺失。 8例分离株中仅 1例带有与HPV 16原毒株相同的 1138位点“G”缺失。结论 在游离态的HPV 16分离株E1/E2区域存在有不同的基因序列重排 ,这可能在病毒致癌方面起一定的作用。

Objective Analysis of genetic situations of E1/E2 region of episomal HPV 16 isolates from cervical carcinomas. Methods Physical statues of HPV 16 DNAs from cervical carcinomas were analyzed by Southern blot hybridization. E1/E2 regions of episomal HPV 16 isolates were amplified by PCR, and the PCR products were cloned and sequenced. Results Eight isolates from totally 28 cases showed extrachromosomal HPV 16 DNA. PCR cloned sequence analysis revealed that all the eight isolates contained intact E1/E2 regions, whereas 4 isolates had different ratios of genetic rearrangements, including insertion of E1 repeat sequence and several deletions. Only one case showed the same G deletion at position 1138 as HPV 16 prototype. Conclusion DNA rearrangements were present in E1/E2 regions of episomal HPV 16 isolates from cervical cancers and might play a role in tumorigenesis. Different viral genotypes in an identical tumor tissue might indicate that the tumor occurring at the same position of a patient may derive from two or even more cell clones.