Frequent epigenetic inactivation of RASSF10 in thyroid cancer.

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.