Accumulation of mitochondrial DNA mutations and their potential roles in the development of papillar

• 作 者: Xingyun Su Weibin Wang Lisong Teng Minxin Guan
• 机 构: Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University,
• 出 处: 2015浙江省肿瘤外科学术年会暨首届钱江国际肿瘤外科高峰论坛
• 发表日期: 2015年8期
• 关键词: Mitochondrial DNA mutation Papillary thyroid cancer Carcinogenesis

　　Background Genetic alterations occurred in etiology and pathogenesis of papillary thyroid cancer (PTC)have been widely investigated.However, the vast majority of researches were concentrated on nuclear genome while less exploration was on mitochondrial genetic determinant.Methods To investigate the mutational spectrum of mitochondrial genome, we directly sequenced the entire mitochondrial DNA (mtDNA) in 18 PTC patients and evaluated the identified variants in databases.The pathogenic potential was assessed by comparing mutation rate in 376 healthy individuals, evolutionary conservation of affected residue, possibly structural influence, and bioinformatic programs.Results We detected 241 alterations in PTCs and most of them were single-base substitutions (230/241,95.4%).Fourteen mutations were not recorded in databases and 10 of them were heteroplasmic.Besides, 15mutations were heteroplasmic and nearly all of them were somatic (14/15, 93.3%).Sixteen variations were assessed to be deleterious which were constituted of 4 alterations in tRNA (3275-3276delCA, A5514G, T5628C,G5881C) and 12 alterations in the coding region including 9 missense mutations (T3644C, C6340T, T7104C,G9804A, G10573A, A13535G, C14774A, T15018A, C15483T), 2 nonsense mutations (T12794A, C14310A), and1 frameshift mutation (12425delA).Conclusions The accumulation of mtDNA alterations can be inherent risk-factors for PTC.These alterations may cause severe structural and functional impairment of mitochondrial complex which contributes to the initiation and progression of PTC.Our study provides promising biomarkers for risk stratification, early detection and possible approaches targeting the mitochondria feasible for PTC.