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Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAF V600E mutation as biomarkers for papillary thyroid carcinoma
Author(s) -
Khatami Fatemeh,
Larijani Bagher,
Heshmat Ramin,
Nasiri Shirzad,
HaddadiAghdam Mohammad,
TeimooriToolabi Ladan,
Tavangar Seyed M.
Publication year - 2020
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.29591
Subject(s) - cancer research , thyroid carcinoma , mutation , v600e , dna methylation , methylation , thyroid cancer , epigenetics , microbiology and biotechnology , promoter , thyroid , papillary thyroid cancer , thyroid nodules , biology , pathology , gene , medicine , gene expression , genetics
Circulating cell‐free DNA (cfDNA) has been considered as a diagnostic source to track genetic and epigenetic alterations in cancer. We aimed to study mutation in addition to the methylation status in the promoter regions of RASSF1 and SLC5A8 genes in tissues and circulating free DNA samples of patients affected with papillary thyroid carcinoma (PTC) and thyroid nodules as controls. BRAF V600E mutation was studied by ARMS‐scorpion real‐time polymerase chain reaction method in 57 PTC and 45 thyroid nodule cases. Methylation status of RASSF1 and SLC5A8 promoter regions was analyzed by methylation‐specific high‐resolution melting curve analysis. BRAF V600E mutation was found in 39 (68.4%) out of 57 PTC tissue samples, while in 33 (49.1%) cases of cfDNA, this mutation was detected. The frequency of BRAF V600E mutation in cfDNA was significantly different between metastatic and nonmetastatic PTC cases (22 of 33 PTC cases vs. 5 of 34 thyroid nodule samples). Methylation levels of three promoter regions of SLC5A8 and proximal promoter region of RASSF1 was significantly different between PTC and thyroid nodule cases in both cfDNA and tissue DNA. In addition, the methylation status of these two genes in tissue DNA was reflected in methylation status observed in cfDNA. This study confirmed that BRAF V600E mutation is better for discrimination between papillary thyroid carcinoma and thyroid nodules. On the other hand, hypermethylation in the more proximal promoter regions to RASSF1 and SLC5A8 genes showed higher sensitivity and more acceptable specificity for this discrimination.