Shi Honghui, Pan Lingya, Song Tian
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, People's Republic of China.
Int J Gynecol Cancer. 2009 Apr;19(3):423-30. doi: 10.1111/IGC.0b013e3181a19ff0.
To investigate somatic mitochondrial DNA mutation in primary and recurrent ovarian carcinoma tissues as well as that in drug-resistant cell lines to illuminate the impact of chemotherapeutic drugs on mitochondrial DNA (mtDNA).
Complete mtDNA genomes of 20 pairs of ovarian carcinomas and their matched normal tissues together with 2 ovarian carcinoma cell lines and their 4 platinum-resistant cell lines were sequenced. Mitochondrial DNA alterations, consequent amino acid alterations were compared between the 2 groups of patients and the 2 types of cell lines.
A large number of mtDNA new polymorphisms (55) and mutations (18) were identified in 20 ovarian carcinoma samples. Platinum-based chemotherapy did not increase the number of new polymorphisms (P = 0.094), mutations (P = 0.688), and consequent amino acid alterations (P = 0.202 and 0.795). Data gained from the cell lines also indicated that platinum had some effect on the mitochondrial genome but not specific to particular positions.
What we found suggested that mtDNA damage could be made by chemotherapeutic drugs but not as much as imagined in ovarian carcinomas. Some of the mtDNA defects might be part of the disease processes and cell properties as well as a consequence of treatment.
研究原发性和复发性卵巢癌组织以及耐药细胞系中的体细胞线粒体DNA突变，以阐明化疗药物对线粒体DNA（mtDNA）的影响。
对20对卵巢癌及其配对的正常组织的完整mtDNA基因组以及2种卵巢癌细胞系及其4种铂耐药细胞系进行测序。比较两组患者和两种细胞系之间的线粒体DNA改变及相应的氨基酸改变。
在20个卵巢癌样本中鉴定出大量mtDNA新多态性（55个）和突变（18个）。铂类化疗并未增加新多态性的数量（P = 0.094）、突变数量（P = 0.688）以及相应的氨基酸改变数量（P = 0.202和0.795）。细胞系的数据也表明铂对线粒体基因组有一定影响，但并非特定于特定位置。
我们的研究结果表明，化疗药物可能会导致mtDNA损伤，但在卵巢癌中损伤程度不如想象的严重。一些mtDNA缺陷可能是疾病进程和细胞特性的一部分，也是治疗的结果。
