嗜酸细胞瘤线粒体DNA非编码控制区基因突变及其意义的初步探讨

Analysis of mitochondrial DNA D-loop region mutation and its significance in human oncocytoma

目的 分析嗜酸细胞瘤中线粒体DNA（mtDNA）非编码控制区（D-loop区）的碱基突变情况及其意义.方法 收集20例甲状腺和肾嗜酸细胞瘤及瘤旁的正常组织石蜡包埋标本,分别提取瘤组织和正常组织的总DNA,对mtDNA D-loop区（1122 bp）进行PCR扩增,以直接测序法检测PCR产物的基因序列.另收集5例人胚胎肾组织作为正常对照.结果 20例甲状腺和肾嗜酸细胞瘤标本中,7例（35.0%）肿瘤组织和1例（5.0%）正常组织共检测出突变位点21个,主要集中在高变区Ⅰ（HVⅠ）.20例（100%）肿瘤标本中均检测出多态性位点,共191个.结论 D-loop区尤其是HV Ⅰ是嗜酸细胞瘤的突变热点,其突变可能引起mtDNA复制速率的变化,并与线粒体功能异常密切相关.

Objective To investigate the mutation in mitochondrial DNA displacement-loop （mtDNA D-loop） region in oncocytoma and its relationship with tumorigenesis and tumor development.Methods The mtDNA D-Loop region of 20 thyoid or renal oncocytomas and the adjacent normal tissues were amplified by PCR, and then sequenced. Five human fetal renal tissues were collected as matched controls. Results Among the 20 oncocytomas, 21 mutations which focused on hypervariable region Ⅰ （ HV Ⅰ ）were found in 7 tumor tissues and 1 normal tissue with the mutation rates of 35% and 5%, respectively. At the same time, 191 polymorphisms were found in the 20 cases. Conclusion mtDNA D-loop region,especiely HV Ⅰ , is the mutational hotspot of oncocytomas, which may be closely related with mtDNA duplicating rate and the function of mitochondria.