Circulating cell-free DNA, SLC5A8 and SLC26A4 hypermethylation, BRAFV600E: A non-invasive tool panel for early detection of thyroid cancer - 09/11/13
, Maria Vittoria Enzo d, Eric Casal Ide a, Paola Del Bianco e, Francesca Torresan a, Isabella Merante Boschin a, Gianmaria Pennelli f, Andrea Saccani g, Domenico Rubello h, Donato Nitti d, Maria Rosa Pelizzo aBienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
Purpose |
In the latest years, high levels of circulating cell-free DNA (cf-DNA) have been found to be associated with cancer diagnosis and progression, and cf-DNA has become a potential candidate as biomarker for tumor detection. cf-DNA has been investigated in plasma or serum of many tumor patients affected by different malignancies, but not yet in thyroid cancer (TC). Furthermore, in TC cells the capability to metabolize iodine is frequently lost. SLC5A8 and SLC26A4 genes are both involved in the iodine metabolism, and SLC5A8 hypermethylation status is associated with the BRAFV600E mutation, which is the most frequent genetic event underlying the development of papillary TC. The aim of our study is the development of a new non-invasive tool for the diagnosis and prognosis of TC based on cf-DNA, SLC5A8 and SLC26A4 hypermethylation, and BRAFV600E analysis.
Methods |
cf-DNA was measured by quantitative real-time PCR in nine cases of anaplastic thyroid cancer (ATC), 58 medullary thyroid cancers (MTC), five of synchronous medullary and follicular thyroid cancers (SMFC), 23 follicular adenomas (FA), 86 papillary thyroid cancers (PTC). A control group of 19 healthy subjects was taken. Moreover, in the PTC group we analyze the state of hypermethylation of SLC5A8 and SLC26A4, BRAFV600E mutation, and their involvement in the loss of function of the thyroid.
Results |
cf-DNA showed a high ability to discriminate healthy individuals from cancer patients. cf-DNAALU83 and cf-DNAALU244 values were significantly correlated with the histological type of TC (P-value<0.0001). A significant increase in the amount of cf-DNAALU83 and cf-DNAALU244 when methylation occurs was observed (P-value=0.02). A correlation between BRAFV600E and cf-DNAALU244/ALU83 was also found (P-value=0.02).
Conclusions |
According to our experimental results, the panel including cf-DNA, SLC5A8 and SLC26A4 hypermethylation, and BRAFV600E analysis appears easy, reproducible, and non-invasive for the diagnosis on TC. Its possible implication in clinical setting remains to be elucidated.
Le texte complet de cet article est disponible en PDF.Keywords : Cell-free-DNA, Thyroid cancers, Methylation, BRAF, Early diagnosis
Plan
Vol 67 - N° 8
P. 723-730 - octobre 2013 Retour au numéro
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