Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782463606859759616 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5085627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT suxingyun acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT wangweibin acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT ruanguodong acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT liangmin acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT zhengjing acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT chenye acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT wuhuiling acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT faheythomasj acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT guanminxin acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT tenglisong acomprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT suxingyun comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT wangweibin comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT ruanguodong comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT liangmin comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT zhengjing comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT chenye comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT wuhuiling comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT faheythomasj comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT guanminxin comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer AT tenglisong comprehensivecharacterizationofmitochondrialgenomeinpapillarythyroidcancer |