<abstract xmlns="http://www.w3.org/1999/xhtml">Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the “pathogenic” A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.</abstract>

Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the “pathogenic” A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma

Department of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of

Department of Endocrinology, Ningbo Fourth Hospital, Xiangshan, People’s Republic of

College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of

School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, People’s Republic of

Department of Clinical Pharmacy, the Affiliated Wenling Hospital of Wenzhou Medial University, Wenling, People’s Republic of

Balkan Journal of Medical Genetics

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

{"article-title":"Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma"}

Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood....

tRNA	tRNA^Asp	tRNA^Arg		tRNA^Leu(CUN)	tRNA^Ile		tRNA^Ala
Nt changes	G7521A	T10411C	T10463C	A12308G	G4292C	C4312T	T5655C
Number of nts in tRNA	4	7	67	44	34	54	1
Position	acceptor arm	acceptor arm	acceptor arm	variable loop	anticodon arm	T arm	acceptor arm
Homoplasmy/heteroplasmy	homoplasmy	homoplasmy	homoplasmy	homoplasmy	homoplasmy	homoplasmy	homoplasmy
CI (%)	13.5	21.1	94.2	93.3	10.0	19.0	71.2
G (wild type)(kcal/mol)	‒10.59	‒10.58	‒10.86	‒16.01	‒8.98	‒8.98	‒18.47
G (mutant)(kcal/mol)	‒11.11	‒10.13	‒10.13	‒15.88	‒9.06	‒9.12	‒18.81

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma

Article Category: Original Article

Pubblicato online: 09 lug 2016

Pagine: 59 - 64

DOI: https://doi.org/10.1515/bjmg-2015-0090

Parole chiave
Association, Mitochondrial DNA (mtDNA), Thyroid cancer, Mitochondrial transfer RNA (mt-tRNA), Variants

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular characterization of mt-tRNA variants for thyroid cancer.

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma

Article Category: Original Article

Pubblicato online: 09 lug 2016

Pagine: 59 - 64

DOI: https://doi.org/10.1515/bjmg-2015-0090

Parole chiaveAssociation, Mitochondrial DNA (mtDNA), Thyroid cancer, Mitochondrial transfer RNA (mt-tRNA), Variants

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular characterization of mt-tRNA variants for thyroid cancer.

Parole chiave
Association, Mitochondrial DNA (mtDNA), Thyroid cancer, Mitochondrial transfer RNA (mt-tRNA), Variants