Endocrine Pathology
Fatemeh Khatami; Bagher Larijani; Ramin Heshmat; Shirzad Nasiri; Hiva Saffar; Gita Shafiee; Azam Mossafa; Seyed Mohammad Tavangar
Abstract
Background & Objective: Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. ...
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Background & Objective: Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. Methylation is the most common type of epigenetic alterations that can be an excellent indicator of PTC invasive behavior. Methods: In this research, we determined the promoter methylation status of four tumor suppressor genes (SLC5A8, RASSF1, MGMT, and DNMT1) and compared the results of 55 PTC cases with 40 goiter patients. For methylation, we used the methylation-sensitive high resolution melting (MS-HRM) assay technique. The resulting graphs of each run were compared with those of 0%, 50%, and 100% methylated controls. Result: Our data showed that the promoter methylation of SLC5A8, Ras association domain family member 1(RASSF1), and MGMT were significantly different between PTC tissue and goiter with P-value less than 0.05. The most significant differences were observed in RASSF1; 77.2% of hyper-methylated PTC patients versus 15.6% hyper-methylated goiter samples (P<0.001). Conclusion: RASSF1 promoter methylation can be a PTC genetic marker. RASSF1 promoter methylation is under the impact of the methyltransferase genes (DNMT1 and MGMT), protein expression, and promoter methylation.
Fahimeh Mousavi; Mehrdad Noruzinia; Elahe Keyhani; Feridoon Seirati; Samira Rezaei; Forough Mojtahedi; Farkhondeh Behjati
Volume 9, Issue 2 , April 2014, , Pages 117-123
Abstract
Background and Objective: The DBC2 (deleted in breast cancer 2) or RhoBTB2 (Located on 8p21) is a tumor suppressor gene associated with tumorigenesis. Mutational studies of DBC2 at its promoter region in breast cancer revealed an important role for epigenetic changes contributing to its low expression. ...
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Background and Objective: The DBC2 (deleted in breast cancer 2) or RhoBTB2 (Located on 8p21) is a tumor suppressor gene associated with tumorigenesis. Mutational studies of DBC2 at its promoter region in breast cancer revealed an important role for epigenetic changes contributing to its low expression. Epigenetic changes through hypermethylation of the promoter can cause the inactivation of DBC2 gene. The purpose of this study was to investigate methylation pattern of DBC2 gene in the peripheral blood of 40 Iranian women with breast cancer and its comparison with healthy women.
Material & Methods: We used peripheral blood samples from 40 patients with sporadic breast cancer and 40 normal individuals. Analysis of the methylation statues of DBC2 promoter region was done by MSP (Methylation Specific PCR ) technique on the DNA extracted from the blood samples. The results were validated by sequencing. The methylation status was then correlated with the clinicopathological parameters of breast cancer patients.
Results:Methylation pattern was detected in 60% of the patients, whereas 25% of the normal individuals demonstrated a positive methylation pattern (P ≤ 0.01, odd ratio : 2.143). No significant correlation was obtained between methylated DBC2 and cliniclpathological parameters.
Discussion: Aberrant hypermethylation was observed preferentially in the patients. These findings along with the previous studies, propose that abnormal methylation pattern in DBC2 promoter region may be one of the main reasons for low expression of DBC2 in breast cancer and this hypermethylation pattern could play a fundamental role in the breast tumorigenesis.
