Aberrant methylation of Rap۱Gap gene promoter in thyroid cancers

Introduction

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.

Methods

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).

Results

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).

Conclusion

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.

References

1. Tetsuo Kondo, Tadao Nakazawa, Defu Ma, et al. Epigenetic silencing of TTF-1/NKX2-1 through DNA hypermethylation and histone H3 modulation in thyroid carcinomas. Lab Invest 2009.
2. Faam B, Ghaffari MA, Ghadiri A, et al. Epigenetic modifications in human thyroid cancers. Biomed Rep, 2015.