Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 25 3 2022 03 01 CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer 171 177 10.34172/aim.2022.29 EN Bita Faam https://orcid.org/0000-0001-5302-3124 Ata. A Ghadiri Mohammad Ali Ghaffari Mehdi Totonchi Atieh Amouzegar Fereidoun Azizi Hajiehbibi Shahbazian Mahmoud Hashemitabar Seyed Ahmad Fanaei Layasadat Khorsandi https://orcid.org/0000-0002-3391-3055 Journal Article 10.34172/aim.2022.29 2020 10 26 2021 02 07 Background: Medullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor. This study aimed to investigate the gene and protein expression of RAP1GAP and DNA methylation patterns of its CpG74a , CpG74b , and CpG24 in an Iranian population with MTC. Methods: In this case-control study, we selected 55 individuals who underwent thyroidectomy in Erfan hospital, Tehran, between 2018 and 2020. Samples were divided into normal thyroid tissues (control; n=20), benign nodule (n=20), and MTC (n=15). DNA methylation patterns were investigated using MSP (methylation-specific PCR). The protein level and mRNA expression of RAP1GAP were also evaluated using western blotting and real-time PCR, respectively. Results: The hyper-methylation rates of CpG24 and CpG74a in the MTC samples were considerably higher than the controls (83% versus 15% and 74% versus 17%, respectively; P<0.001). The methylation/unmethylation ratio of CpG74a , and CpG24 was considerably higher than the controls (P<0.001). The methylation/unmethylation ratio of CpG24 in the benign nodules was also considerably greater than the controls (P<0.001). The mRNA expression and the protein level of RAP1GAP in the MTC group were considerably lower than the controls (P=0.005 and P=0.035, respectively). In the MTC group, aberrant methylation of CpG74a and CpG24 was significantly correlated with decreasing expression of the Rap1Gap gene (R2 : 0.23; P=0.032 and R2 : 0.56; P=0.001, respectively). Conclusion: Hyper-methylation in CpG24 and CpG74a and decreasing expression of RAP1GAP can be considered as diagnostic biomarkers for MTC.