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Int. J. Mol. Sci. 2016, 17(10), 1594; doi:10.3390/ijms17101594

A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer

1
Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
2
Department of Oncology, the Second Hospital of Shaoxing, Shaoxing 312000, China
3
Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China
4
Department of Plastic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
5
Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniela Gabriele Grimm
Received: 5 July 2016 / Revised: 17 August 2016 / Accepted: 8 September 2016 / Published: 10 October 2016
(This article belongs to the Special Issue Current Knowledge in Thyroid Cancer—From Bench to Bedside)
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Abstract

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. View Full-Text
Keywords: mitochondrial DNA; mitochondrial DNA copy number; haplogroup; papillary thyroid cancer mitochondrial DNA; mitochondrial DNA copy number; haplogroup; papillary thyroid cancer
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Su, X.; Wang, W.; Ruan, G.; Liang, M.; Zheng, J.; Chen, Y.; Wu, H.; Fahey, T.J., III; Guan, M.; Teng, L. A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer. Int. J. Mol. Sci. 2016, 17, 1594.

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