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Investigating the expression and promoter methylation of RET gene in patients with medullary thyroid cancer with unmutated RET
Author(s) -
Shakiba Elham,
Movahedi Monireh,
Majd Ahmad,
Hedayati Mehdi
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28295
Subject(s) - medullary thyroid cancer , epigenetics , exon , methylation , cancer research , dna methylation , proto oncogene proteins c ret , promoter , biology , gene , pheochromocytoma , microbiology and biotechnology , cancer , genetics , medicine , thyroid cancer , gene expression , receptor , neurotrophic factors , glial cell line derived neurotrophic factor
Objective Thyroid cancer is one of the most common endocrine malignancies. Mutations in the rearranged during transfection (RET) gene, especially in exon 10, 11, and 16, as well as epigenetic modifications, constitute the major underlying molecular events leading to medullary thyroid cancer (MTC). There are few studies on the mutations and epigenetic changes of RET gene in Iranian patients with MTC. In the present study, we aimed to address this question and explore the clinical relevance of such genetic alternations in an Iranian population. Methods Thirty‐three patients with confirmed MTC who underwent thyroidectomy surgery in Imam Khomeini Hospital (Tehran, Iran) were enrolled. DNA extracted from cancerous tissues was amplified by polymerase chain reaction (PCR) and then was sequenced for identification of RET mutations. In patients with no identified mutations, the methylation status of RET promoter and its expression were further investigated using methylation‐specific PCR and real‐time PCR methods, respectively. Results In MTC patients with no RET mutations, the promoter of the proto‐oncogene was hypomethylated. Furthermore, RET gene expression was elevated in patients who revealed no mutations in neither of exon 10, 11, or 16 of the RET gene. Conclusion Hypomethylation of RET promoter may contribute to MTC pathogenesis. The methylation status of RET promoter could be a new potential prognostic, diagnostic and therapeutic marker in MTC.