Frequent epigenetic inactivation of RASSF10 in thyroid cancer
Frequent epigenetic inactivation of RASSF10 in thyroid cancer
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DOI：
10.4161/epi.4.8.10056
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发表时间：
2009-11-16
期刊：
影响因子：
3.7
通讯作者：
Dammann, Reinhard H.
中科院分区：
文献类型：
--
作者：
Schagdarsurengin, Undraga;Richter, Antje M.;Dammann, Reinhard H.
RAS相关结构域家族(RASSASSASSF)编码不同的肿瘤抑制因子，其中几个成员在人类癌症中经常被沉默。在我们的研究中，我们分析了一个新的名为RASSF10的RASSASSASSF成员在甲状腺癌发生中的作用。RASSF10 CpG岛启动子在9个甲状腺癌细胞系和66%的原发性甲状腺癌中高度甲基化。RASSF10甲基化在原发性甲状腺癌中显著高于正常甲状腺和滤泡性腺瘤(分别为0%和10%；p<；0.004)。在原发性甲状腺肿瘤中，有癌淋巴结的患者RASSF10的甲基化程度显著高于未受影响的淋巴结患者(79%vs.36%；p=0.047)。RASSF10启动子高甲基化与表达减少相关，用DNA甲基化抑制剂处理后重新激活RASSF10转录。综上所述，我们的数据显示RASSF10在甲状腺癌中频繁的表观遗传学失活。这些结果提示，RASSF10可能编码一个新的表观遗传学失活的候选抑癌基因，参与甲状腺癌的发生。
The Ras association domain family (RASSASSASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of a novel RASSASSASSF member termed RASSF10 in thyroid carcinogenesis. The RASSF10 CpG island promoter was intensively methylated in nine thyroid cancer cell lines and in 66% of primary thyroid carcinomas. RASSF10 methylation was significantly increased in primary thyroid carcinoma compared to normal thyroid and follicular adenoma (0% and 10%, respectively; p < 0.004). Patients with cancerous lymph nodes were significantly hypermethylated for RASSF10 in primary thyroid tumors compared to those with non-affected lymph nodes (79% vs. 36%; p = 0.047). RASSF10 promoter hypermethylation correlated with a reduced expression and treatment with a DNA methylation inhibitor reactivated RASSF10 transcription. In summary, our data show frequent epigenetic inactivation of RASSF10 in thyroid cancer. These results suggest that RASSF10 may encode a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis.