Journal
EPIGENETICS
Volume 4, Issue 8, Pages 571-576Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/epi.4.8.10056
Keywords
thyroid cancer; Ras association domain family; tumor suppressor gene; epigenetics; DNA methylation
Funding
- Deutsche Krebshilfe [107742]
- Deutsche Forschungsgemeinschaft (DFG) [DA552]
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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.
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