肺癌中p53基因突变分析及人乳头瘤病毒检测

POINT MUTATION OF p53 AND DETECTION OF HUMAN PAPILLOMAVIRUS DNA IN BRON CHOGENIC CARCINOMA

拟从分子生物学水平探讨肺癌的早期诊断问题。实验采用ｐ５３基因中第６，７，８外显子各设计一对引物，对３４例肺癌手术标本进行聚合酶链反应扩增（ＰＣＲ），产物经聚丙烯酰胺凝胶电泳进行单链构象多态性分析（ｓｉｎｇｌｅ－ｓｔｒａｎｄ－ｃｏｎｆｏｒｍａｔｉｏｎ－ｐｏｌｙｍｏｒ－ｐｈｉｓｍ，ＳＳＣＰ），发现３０例发生突变，突变率为８８．２％，其中鳞癌１０／１２例，腺癌８／１０例，小细胞癌３／３例，大细胞癌１／１例，肺泡细胞癌５／５例，腺鳞癌３／３例。在突变的１例鳞癌中同时伴有杂合性缺失。统计学分析表明，ｐ５３突变与组织分型、分化程度、临床分期及吸烟史无密切相关。提示ｐ５３突变在肺癌发生过程中起某种作用，可能主要影响肺癌发生的早期。本实验还运用多重引物ＰＣＲ方法对３４例肺癌标本进行人乳头瘤病毒（ＨＰＶＤＮＡ）检测，发现４例阳性，且皆为鳞癌；而其中３例检测出ｐ５３突变。

he p53 gene has been implicated in the pathogenesis of lung cancer as a tumor suppressor gene. Abrrations of the p53 gene(exon 6～8)were examined in 34 surgical specimens of lung cancer with sin- gle-strand-conformation-polymorphism analysis of polymerase chain reaction products,Structural abnor- malities of the p53 gene were observed in 30 tumor specimens(88.2%),i.e,in 10 of the 12 specimens with squamous cell carcinoma, 8 of the 10 with adenocarcinoma,all the 3 small cell carcinoma,the only one large cell carcinoma,all the 5 alveolar cell carcinoma and a11 the 3 adenosquamous carcinoma. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage and were not associated with degree of differentiation or history of heavy smoking.It is suggested that high mutation rate of the p53 gene may participate in the genesis of lung cancer.In this study multiple primer poly- merase chain reaction method was applied to detect the human papillomavirus DNA(HPV DNA)in human lung cancer.Only 4 of these 34 specimens were HPV DNA positive,and they were all of squamous cell carcinoma,3 of them had p53 mutation.