Endocrine Abstracts

Background: It is currently present in the literature that mitochondrial DNA (mtDNA) defects are associated with a great number of diseases including cancers. The role of mitochondrial DNA (mtDNA) mutations/variations in the development of thyroid cancers is a highly controversial topic. In this study, we aimed to investigate the role of mt-DNA control region (CR) variations in thyroid tumor occurrence and the influence of mtDNA haplogroups on susceptibility to thyroid tumors in Turkish population.

Material and method: For this purpose, totally 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subject’s blood samples were screened for entire mtDNA CR variations. MtDNA D-loop CR was screened by using Sanger sequencing. The obtained DNA sequences were evaluated and mitohaplogroups were determined with the mitomaster, a web-based bioinformatics tool.

Results: MtDNA haplogroup U was significantly associated with susceptibility to benign and malign thyroid entities on the other hand J haplogroup was associated with a protective role for benign thyroid nodules. Besides, 10 SNPs (T146C, G185A, C194T, C295T, D568, G16129A, C16292T, T16304C, A16343G and T16362C) in mtDNA CR were associated with the occurrence of benign and malign thyroid nodules in Turkish population. By contrast with the healthy Turkish population and HTNs, the frequency of C7 repeats in D310 polycytosine sequence was found higher in CTN and PTC samples (χ² test; P=0.04) Beside this, the frequency of somatic mutations in MSI regions including T16189C and D514 CA dinucleotide repeats were found higher in PTC samples than the benign thyroid nodules (χ² test; P<0.0001, P=0.0003 respectively). Conversely, the frequency of somatic mutations in D310 MSI was detected higher in HTNs than CTNs and PTCs (P=0.04).

Conclusion: This study reveals that U haplogrup is associated with the susceptibility to benign and malign thyroid tumor occurrence in Turkish population. Although mtDNA D310 instability does not play a role in tumorigenesis of the PTC, the results indicates that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. Beside this, D514 CA instability might be also used as prognostic biomarker in PTCs.