Promoter Hypermethylation Analysis of the Tumor Suppressor Genes RASSF1A and RASSF2A in Iranian Endometrial Carcinoma Patients

Abstract

Introduction: The endometrial cancer (EC) is the seventh most common malignancies worldwide among females with good prognosis in early stages of the disease. The CpG Island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we investigated the methylation pattern in promoter region of RASSF1A and RASSF2A genes in Endometrial cancer patients in Iranian women to identify correlations among promoter hypermethylation, disease risk and clinicopathological parameters. Methods: 28 patients and 22 healthy controls were studied. Isolation of genomic DNA from FFPE and peripheral blood was performed and Methylation-Specific PCR (MSP) was applied for analysis of the promoter CpG methylation status of RASSF1A and RASSF2A genes in the studied population. Results: A significant difference was found among the study groups and the presence of promoter CpG hypermethylation status in the RASSF1A (P = 0.0321) and RASSF2A (P = 0.0003) genes. RASSF1A, and RASSF2A gene promoter methylations were present in 53.57% and 42.85% of EC samples when compared to those in the controls with 31.81% and 9.09% respectively. Furthermore, methylation status between tissue and blood samples of RASSF1A, and RASSF2A genes was not significant (P = 0.49 and 0.09 respectively). Our results indicated a corollation between ages, menosososal state and tumor grade with RASSF1A, and RASSF2A promoter methylation. Conclusions: In our study, Hypermethylation of both RASSF1A and RASSF2A genes are important events in carcinogenesis of endometrial cancer. Epigenetic alternations may have diagnostic value for early diagnosis and better clicinal management of susceptibility to endometrial malignancies.