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

Autor: Cenk Aral, Sukran Sarikaya, Serhat Özçelik, Hulya Iliksu Gozu, Aylin Ege Gul, Rifat Bircan, Esra Ulu, Duygu Yasar Sirin
Přispěvatelé: Bircan, Rifat, Gozu, Hulya Iliksu, Ulu, Esra, Sarikaya, Sukran, Gul, Aylin Ege, Sirin, Duygu Yasar, Ozcelik, Serhat, Aral, Cenk
Rok vydání: 2019
Předmět:
0301 basic medicine
Identification
endocrine system diseases
Endocrinology
Diabetes and Metabolism
mitochondrial DNA
D-LOOP REGION
medicine.disease_cause
Haplogroup
Papillary thyroid cancer
0302 clinical medicine
Endocrinology
Thyroid cancer
POPULATION
Nodules
D310
Thyroid
Instability
T16189C
General Medicine
control region
D514 CA repeat
medicine.anatomical_structure
thyroid nodule
MOLECULAR PATHOGENESIS
Mutations
Receptor
Thyroid nodules
Mitochondrial DNA
Evolution
Population
INSTABILITY
030209 endocrinology & metabolism
Single-nucleotide polymorphism
Biology
Thyroid carcinoma
03 medical and health sciences
NODULES
Germline mutation
Internal Medicine
medicine
D-Loop Region
papillary thyroid cancer
POLYMORPHISMS
RECEPTOR
IDENTIFICATION
MUTATIONS
medicine.disease
Molecular Pathogenesis
EVOLUTION
030104 developmental biology
Tumor progression
Cancer research
Polymorphisms
Carcinogenesis
Human mitochondrial DNA haplogroup
Zdroj: Experimental and Clinical Endocrinology & Diabetes. 127:423-436
ISSN: 1439-3646
0947-7349
DOI: 10.1055/a-0869-7355
Popis: BackgroundIt 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) variations in the development of thyroid cancer is a highly controversial topic. In this study, 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.Material & methodFor 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 by using Sanger sequencing. The obtained DNA sequences were anaysed with the mistomaster, a web-based bioinformatics tool.ResultsMtDNA 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, 8 SNPs (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in mtDNA CR region were associated with the occurrence of benign and malign thyroid nodules in Turkish population. By contrast with the healthy Turkish population and HTNs, frequency of C7 repeats in D310 polycytosine sequence was found higher in cold thyroid nodules and PTC samples. Beside this, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found higher in PTC samples than the benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was detected higher in HTNs than CTNs and PTCs.ConclusionmtDNA D310 instability do not play a role in tumorogenesis of the PTC but 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 used as prognostic biomarker in PTCs. Also, we showed that somatic mutation rate is less frequent in more aggressive tumors when we examined micro- and macro carcinomas as well as BRAFV600E mutation.
Databáze: OpenAIRE
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