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A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer

Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. The...

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Autores principales: Su, Xingyun, Wang, Weibin, Ruan, Guodong, Liang, Min, Zheng, Jing, Chen, Ye, Wu, Huiling, Fahey, Thomas J., Guan, Minxin, Teng, Lisong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085627/
https://www.ncbi.nlm.nih.gov/pubmed/27735863
http://dx.doi.org/10.3390/ijms17101594
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author Su, Xingyun
Wang, Weibin
Ruan, Guodong
Liang, Min
Zheng, Jing
Chen, Ye
Wu, Huiling
Fahey, Thomas J.
Guan, Minxin
Teng, Lisong
author_facet Su, Xingyun
Wang, Weibin
Ruan, Guodong
Liang, Min
Zheng, Jing
Chen, Ye
Wu, Huiling
Fahey, Thomas J.
Guan, Minxin
Teng, Lisong
author_sort Su, Xingyun
collection PubMed
description Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. There were 2508 variations (543 sites) detected in PTCs, among which 33 variations were novel. Nearly half of the PTCs (31/66) had heteroplasmic variations. Among the 31 PTCs, 28 specimens harbored a total of 52 somatic mutations distributed in 44 sites. Thirty-three variations including seven nonsense, 11 frameshift and 15 non-synonymous variations selected by bioinformatic software were regarded as pathogenic. These 33 pathogenic mutations were associated with older age (p = 0.0176) and advanced tumor stage (p = 0.0218). In addition, they tended to be novel (p = 0.0003), heteroplasmic (p = 0.0343) and somatic (p = 0.0018). The mtDNA copy number increased in more than two-third (46/66) of PTCs, and the average content in tumors was nearly four times higher than that in adjacent normal tissues (p < 0.0001). Three sub-haplogroups of N (A4, B4a and B4g) and eight single-nucleotide polymorphisms (mtSNPs) (A16164G, C16266T, G5460A, T6680C, G9123A, A14587G, T16362C, and G709A) were associated with the occurrence of PTC. Here we report a comprehensive characterization of the mitochondrial genome and demonstrate its significance in pathogenesis and progression of PTC. This can help to clarify the molecular mechanisms underlying PTC and offer potential biomarkers or therapeutic targets for future clinical practice.
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spelling pubmed-50856272016-11-01 A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer Su, Xingyun Wang, Weibin Ruan, Guodong Liang, Min Zheng, Jing Chen, Ye Wu, Huiling Fahey, Thomas J. Guan, Minxin Teng, Lisong Int J Mol Sci Article Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. There were 2508 variations (543 sites) detected in PTCs, among which 33 variations were novel. Nearly half of the PTCs (31/66) had heteroplasmic variations. Among the 31 PTCs, 28 specimens harbored a total of 52 somatic mutations distributed in 44 sites. Thirty-three variations including seven nonsense, 11 frameshift and 15 non-synonymous variations selected by bioinformatic software were regarded as pathogenic. These 33 pathogenic mutations were associated with older age (p = 0.0176) and advanced tumor stage (p = 0.0218). In addition, they tended to be novel (p = 0.0003), heteroplasmic (p = 0.0343) and somatic (p = 0.0018). The mtDNA copy number increased in more than two-third (46/66) of PTCs, and the average content in tumors was nearly four times higher than that in adjacent normal tissues (p < 0.0001). Three sub-haplogroups of N (A4, B4a and B4g) and eight single-nucleotide polymorphisms (mtSNPs) (A16164G, C16266T, G5460A, T6680C, G9123A, A14587G, T16362C, and G709A) were associated with the occurrence of PTC. Here we report a comprehensive characterization of the mitochondrial genome and demonstrate its significance in pathogenesis and progression of PTC. This can help to clarify the molecular mechanisms underlying PTC and offer potential biomarkers or therapeutic targets for future clinical practice. MDPI 2016-10-10 /pmc/articles/PMC5085627/ /pubmed/27735863 http://dx.doi.org/10.3390/ijms17101594 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Su, Xingyun
Wang, Weibin
Ruan, Guodong
Liang, Min
Zheng, Jing
Chen, Ye
Wu, Huiling
Fahey, Thomas J.
Guan, Minxin
Teng, Lisong
A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title_full A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title_fullStr A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title_full_unstemmed A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title_short A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
title_sort comprehensive characterization of mitochondrial genome in papillary thyroid cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085627/
https://www.ncbi.nlm.nih.gov/pubmed/27735863
http://dx.doi.org/10.3390/ijms17101594
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