PTEN promoter methylation in sporadic thyroid carcinomas
PTEN promoter methylation in sporadic thyroid carcinomas
复制标题
DOI：
10.1089/thy.2006.16.17
复制
发表时间：
2006-01-01
期刊：
影响因子：
6.6
通讯作者：
Matias-Guju, X
中科院分区：
文献类型：
--
作者：
Alvarez-Nuñez, F;Bussaglia, E;Matias-Guju, X
位于染色体10q23.3上的抑癌基因PTEN/MMAC1与许多重要的人类肿瘤有关，如甲状腺癌。PTEN体细胞突变发生在子宫内膜、脑、前列腺或黑色素瘤的零星肿瘤中，而胚系突变则易发生多发性错构瘤综合征(即考登氏病和Bannayan-Zonana综合征)。PTEN的肿瘤抑制作用需要激活PTEN的两个等位基因。由于PTEN在甲状腺肿瘤中的抑制频率高于PTEN突变或缺失的频率，因此很可能是表观遗传机制，如启动子超甲基化，可能是导致PTEN在一组肿瘤中失活的原因。本研究的主要目的是评估甲状腺肿瘤中PTEN基因启动子高甲基化的频率。我们研究了46例乳头状癌、7例滤泡性癌、6例滤泡性腺瘤以及39例正常甲状腺组织的冰冻组织标本。用三套不同的引物进行甲基化特异性聚合酶链式反应(PCR)。其中两套设计用于避免与PTEN假基因启动子的干扰。46例乳头状癌中21例(45.7%)、7例滤泡性癌中6例、滤泡性腺瘤中5例PTEN启动子甲基化。在正常组织中均为阴性。PTEN免疫组织化学染色阴性与启动子高甲基化显著相关(p<；0.001)。这些结果表明PTEN启动子高甲基化的频率很高，特别是在滤泡性肿瘤中，提示它可能在甲状腺肿瘤的发生中起作用。
The tumor-suppressor gene PTEN/MMAC1, on chromosome 10q23.3, has been implicated in an important number of human tumors, such as thyroid carcinomas. PTEN somatic mutations occur in sporadic tumors of the endometrium, brain, prostate, or melanomas, while germline mutations predispose to development of the multiple hamartoma syndromes (i.e., Cowden's disease and Bannayan-Zonana syndrome). Activation of the two alleles of PTEN is required for its tumor-suppression role. Because the frequency of PTEN suppression in thyroid tumors exceeds that of PTEN mutations or deletions, it is very likely that epigenetic mechanisms, such as promoter hypermethylation, may account for its inactivation in a subset of tumors. The main aim of this study was to assess the frequency of promoter hypermethylation of PTEN in thyroid tumors. We studied frozen tissue samples from 46 papillary carcinomas, 7 follicular carcinomas, 6 follicular adenomas as well as 39 normal thyroid tissue samples. Methylation-specific polymerase-chain reaction (PCR) with three different sets of primers was used. Two of the primer sets were designed to avoid any interference with PTEN pseudogene promoter. PTEN promoter hypermethylation was detected in 21 of 46 (45.7%) papillary carcinomas, 6 of 7 follicular carcinomas, and 5 of 6 follicular adenomas. It was negative in all normal tissues. Negative immunohistochemical staining for PTEN was significantly associated with the presence of promoter hypermethylation (p < 0.001). These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis.