Assessment of RET Gene Promoter Methylation in Medullary Thyroid Cancer Patients without RET mutation

Thyroid cancer is one of the most common endocrine malignancies. There is no effective treatment for progressed thyroid cancer that does not respond to radioiodine therapy. Medullary thyroid cancer (MTC (involves 5% of thyroid cancers. The primary mechanism of tumorigenicity of the medullary thyroid carcinoma is the inactivation of the RET protoncogene signaling, which is caused by a mutation in this gene. MTC is described by a mutation in the RET gene. These mutations are clustered in 10, 11 and 16 exons predominantly.Epigenetic changes are common in human cancer cells. Epigenetic factors such as DNA methylation play an important role in regulating gene expression. Aberrant DNA methylation is a feature of a number of important human diseases. Decreased methylation, and hence relief of transcriptional silencing, may allow the expression of previously quiescent proto-oncogenes to become active and induce the cell proliferation events.Methods: 33 patients who underwent thyroidectomy surgery in Tehran Imam Khomeini hospital, with confirmed MTC by the pathologist, were examined. Tissue mutations of the RET were determined. DNA which was extracted from tissues were amplified by PCR and then sequenced. The methylation of RET promoter was assessed using MSP method in non-mutated patients.Conclusion: RET protooncogene in the patients without mutation showed hypomethylation respective to the normal group. The normal group was amplified with both methylated and unmethylated primer pairs but the patients group mostly amplified with an unmethylated pair. This could imply that hypomethylation in RET promoter may be effective in this type of malignancy.RET promoter methylation could be a new marker for prognosis, diagnosis, and treatment for MTC.

کلیدواژه ها:

RET protooncogene ، methylation ، medullary thyroid carcinoma ، cancer