Institute for Genetics, Justus-Liebig-University, Giessen, Germany.
Epigenetics. 2009 Nov 16;4(8):571-6. doi: 10.4161/epi.4.8.10056. Epub 2009 Nov 14.
The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of a novel RASSF 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.
Ras 相关结构域家族（RASSF）编码了不同的肿瘤抑制因子，其中一些成员在人类癌症中经常失活。在我们的研究中，我们分析了一种称为 RASSF10 的新型 RASSF 成员在甲状腺癌发生中的作用。RASSF10 的 CpG 岛启动子在 9 种甲状腺癌细胞系和 66%的原发性甲状腺癌中被强烈甲基化。与正常甲状腺和滤泡性腺瘤相比，RASSF10 甲基化在原发性甲状腺癌中显著增加（分别为 0%和 10%；p<0.004）。与无淋巴结受累的患者相比，患有癌性淋巴结的患者在原发性甲状腺肿瘤中 RASSF10 的甲基化明显增加（79%比 36%；p=0.047）。RASSF10 启动子的高甲基化与表达降低相关，而 DNA 甲基化抑制剂的治疗可重新激活 RASSF10 的转录。总之，我们的数据显示 RASSF10 在甲状腺癌中经常发生表观遗传失活。这些结果表明，RASSF10 可能编码一种在甲状腺癌发生中新型的表观遗传失活候选肿瘤抑制基因。
