The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

The literature suggests that mitochondrial DNA (mtDNA) defects are associated with a large number of diseases including cancers. The role of mtDNA variations in thyroid cancer is a highly controversial topic. Therefore, we investigated the role of mt-DNA control region (CR) variations in thyroid tumor progression and the influence of mtDNA haplogroups on susceptibility to thyroid tumors. For this purpose, in total, 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subjects' blood samples were screened for all mtDNA CR variations using Sanger sequencing. We found that MtDNA haplogroup U was significantly associated with susceptibility to benign thyroid entities. In addition, eight single nucleotide polymorphisms (SNPs) (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in the mtDNA CR were associated with the occurrence of benign and malign thyroid nodules in the Turkish population. As compared with samples taken from a healthy Turkish population and HTNs, the frequency of C7 repeats in D310 polycytosine sequence was found to be higher in CTNs and the PTC samples. In addition, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found to be higher in PTC samples than benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was found to be higher in HTNs than CTNs and PTCs. In conclusion, mtDNA D310 instability does not play a role in the tumorigenesis of PTC but the results indicate that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. In addition, D514 CA instability might be considered as a prognostic biomarker for benign to malign transformation in thyroid tumors.Research Fund of the Tekirdag Namik Kemal University [NKUBAP.00.10.AR.14.07, NKUBAP.00.10.AR.15.05]This work was supported by two grants from the Research Fund of the Tekirdag Namik Kemal University, project numbers NKUBAP.00.10.AR.14.07 and NKUBAP.00.10.AR.15.05

Is the TSHR D727E polymorphism a genetic predisposition for multinodular goiter in the Turkish population?

The D727E germline polymorphism in the thyroid-stimulating hormone receptor gene (TSHR) may cause genetic susceptibility to the development of goiter. Therefore, in this study we investigated allele frequencies and genotype distributions of the TSHR D727E polymorphism, their association with clinical parameters, and the development of goiter in the Turkish population. We investigated the TSHR D727E polymorphism in 123 patients and 97 healthy subjects using the polymerase chain reaction-restriction fragment length polymorphism technique. Peripheral blood was used for DNA extraction. Although no significant difference was found in TSHR D727E polymorphism frequencies between the patients with nodular goiters (26/123 patients, 21.1%) and the controls (12/97 patients, 12.4%) (P = 0.107), the frequency of the TSHR D727E polymorphism in the hyperthyroid+ subclinical hyperthyroid patient groups (23%) was significantly higher than in the control subjects (12.4%) (P = 0.024). In this study, nodular goiter presented significantly earlier in GC genotype patients (mean age 35 years) than in CC genotype patients (mean age 42 years) in the hyperthyroid group (P = 0.009). More importantly, TSH levels in the GC variant controls were closely significant lower (1.26 +/- 0.49) than in the CC variant controls (1.74 +/- 0.84) (P = 0.053). The TSHR D727E polymorphism might be involved in the pathogenesis of toxic multinodular goiter (TMNG). Moreover, this polymorphism might be an indication of early-onset TMNG. However, development of MNG is multifactorial. Therefore, further case-control studies with larger populations are required to verify these observations