A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
AbstractNuclear 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
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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.
Su X, Wang W, Ruan G, Liang M, Zheng J, Chen Y, Wu H, Fahey TJ, III, Guan M, Teng L. A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer. International Journal of Molecular Sciences. 2016; 17(10):1594.Chicago/Turabian Style
Su, Xingyun; Wang, Weibin; Ruan, Guodong; Liang, Min; Zheng, Jing; Chen, Ye; Wu, Huiling; Fahey, Thomas J., III; Guan, Minxin; Teng, Lisong. 2016. "A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer." Int. J. Mol. Sci. 17, no. 10: 1594.
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