Thyroid carcinoma is the most common endocrine malignancy in worldwide. Hypermethylation of suppressor genes considered as the hallmark of cancers. Rap1Gap as a suppresser gene is implicated in the regulation of oncogenic pathways in thyroid carcinoma. The objective of this study was to examine the DNA methylation pattern of Rap1Gap gene in thyroid carcinoma.
We analyzed 95 thyroid tumor samples including normal thyroid (28 cases), benign nodules (29 cases), papillary thyroid cancer (PTC) (29 cases), follicular thyroid cancer (FTC) (6 cases) and Anaplastic thyroid cancer (ATC) (3 cases) from Erfan grand hospital, Tehran, Iran. Rap1Gap gene expression was assessed using SYBR Green Real-Time PCR. CpG24 Island within Rap1Gap promoter region was selected; DNA methylation pattern was examined using methylation specific PCR (MSP).
This study showed that Rap1Gap was frequently lost or downregulated in various types of tumors, particularly in the most invasive and aggressive forms of thyroid cancer. Downregulation could be related to promotor hypermethylation. DNA methylation was identified in 21% of normal tissues, 86% of benign nodules, 90% of differentiated tumors (PTC, FTC) and 100% of undifferentiated tumors (ATC).
The result of this study demonstrates that Rap1Gap is likely to serve as an important tumor suppresser gene in thyroid cells and its loss during aberrant methylation contributes to tumor progression and invasion.