非小细胞肺癌pl6/CDKN2基因失活的研究  

Studies on Inactivation of p16/CDKN2 Gene in Non-Small Cell Lung Cancer

作　　者：安倩[1,2] 董向阳[1,2] 张建军[1,2] 黄进丰[1,2] 李立[2] 程书钧[1,2] 高燕宁[1,2] 

机构地区：[1]中国协和医科大学 [2]中国医学科学院肿瘤研究所

出　　处：《癌症》2001年第6期591-594,共4页Chinese Journal of Cancer

基　　金：国家"九五"攻关项目基金(编号:96-906-01-14);国家重点基础研究发展规划项目基金("973"课题;编号:G1998

摘　　要：目的：分析中国人非小细胞肺癌中ｐ１６／ＣＤＫＮ２基因失活的情况，探讨该基因在肺癌发生中的作用。方法：选取与ｐ１６基因紧密连锁的Ｄ９Ｓ１７４８位点，对１７例临床切除的原发性肺癌标本进行微卫星不稳定性分析，用甲基化特异性ＰＣＲ（ｍｅｔｈｙｌａｔｉｏｎ－ｓｐｅｃｉｆｉｃ ＰＣＲ， ＭＳＰ）检测 ｐｌ６基因启动子区 ＣｐＧ岛甲基化状况，用免疫组织化学法检测Ｐ１６蛋白表达情况。结果：微卫星不稳定性分析结果表明，在１３例Ｄ９Ｓ１７４８位点存在多态性的肿瘤ＤＮＡ中有 ９例（６９ ．２％）发生了杂合性缺失（ｌｏｓｓ ｏｆ ｈｅｔｅｒｏｚｙｇｏｓｉｔｙ， ＬＯＨ）。 ＭＳＰ的结果显示，有 ７０． ６％（１２／１７）的肿瘤组织存在ｐ１６启动子区的异常高甲基化。在本研究中，８２．４％（１４／１７）的肿瘤组织可以检测出一种或两种ｐ１６基因的异常改变。对此１７例肿瘤标本进行的免疫组织化学分析显示，有 １３例 Ｐ１６蛋白表达阴性，其中 ９２ ３％（１２／１３）存在一种或两种ｐ１６基因的异常改变。免疫组化结果与ｐ１６基因分子遗传学改变情况基本吻合。结论：作为一种抑癌基因，ｐ１６在多种肿瘤组织中都有异常改变。我们的研究表明，ｐ１６基因失表达是非小细胞肺癌?Objective: This study was designed to investigate the mechanisms of the p16 inactivation in Chinese non-small cell lung cancer (NSCLC) patients and the role of the pl6 as a tumor suppressor gene (TSG) in the genesis of Chinese NSCLC. Method: The genetic and epigenetic alterations of pl6 gene were examined in 17 cases of primary lung cancers by using the methods of microsatellite analysis and methylation-specific PCR (MSP), and P16 protein expression was determined with immunohistochemical staining (IHC). ResultS: Among 13 informative cases, 9 (69. 2% ) had loss of heterozygosity (LOH) for D9S1748, the closest flanking marker to pl6 gene. Among 17 tumor samples, 12 (70. 6% ) displayed promoter methylation from MSP analysis. In total, 82. 4% (14/17 ) of the cases had one or two genetic/ epigenetic alterations of pl6 gene. The results from IHC indicated that 76. 5% (13/17) of these tumor samples had negative P16 protein expression. Among these pl6 protein negative cases, 92. 3% (12/ 13 ) carried at least one of these aberrations. The data showed a good correlation between the results of IHC and molecular analyses. Conclusion: This study suggests that the pl6 may play a critical role in the genesis of Chinese NSCLC, and loss of one allele in addition to promoter hypermethylation of another allele is the main mechanism of the p16 inactivation, which could be useful techniques for early detection of NSCLC.

关 键 词：非小细胞肺癌 p16/CDKN2基因 基因失活 肿瘤病理学 

分 类 号：R734.2[医药卫生—肿瘤] R730.2[医药卫生—临床医学]