【摘 要】
:
乙型肝炎病毒(HBV)相关的肝癌组织中普遍存在HBV基因组整合的现象,但是其与肝癌发病年龄的关系未见系统研究,对肝癌发生、发展、转移过程的影响机制也尚未阐明.本项目组研究采用一种新的高通量病毒整合检测方法(HIVID)进行筛选,经过对测序结果分析后,我们发现早发性肝癌的6个样品中总共有97个乙肝病毒整合位点而晚发性肝癌的6个样品中有104整合位点.然后,我们针对获得的整合位点采用PCR和测序的方法
【机 构】
:
第二军医大学基础部医学遗传学教研室 上海200433
论文部分内容阅读
乙型肝炎病毒(HBV)相关的肝癌组织中普遍存在HBV基因组整合的现象,但是其与肝癌发病年龄的关系未见系统研究,对肝癌发生、发展、转移过程的影响机制也尚未阐明.本项目组研究采用一种新的高通量病毒整合检测方法(HIVID)进行筛选,经过对测序结果分析后,我们发现早发性肝癌的6个样品中总共有97个乙肝病毒整合位点而晚发性肝癌的6个样品中有104整合位点.然后,我们针对获得的整合位点采用PCR和测序的方法对混合样品中每个单独的样品进行检测.最终我们在24例早发性肝癌的患者样本中成功验证了76个位点(78.4%,76/97)和在28例晚发性患者的样本中验证得到了84个位点(80.8%,84/106).提示HBV整合在早发和晚发性两种肝癌中都普遍发生.并且这些检测到HBV整合的位点是随机分布在整个基因组,同时我们还发现两组样本中存在少数热点位置的差异,在早发组,乙肝病毒常常整合到SYT12,GATM,FN1基因和MYC和PVT1之间的基因间区域.这表明,可能是在早发性肝癌中可能存在特异性的整合位点.因此,本课题研究有助于阐明肝癌早发的发病机制,并为寻找早发性肝癌早期诊断、治疗新靶点提供理论基础和方向.
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