Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1) were quantified in 62 cancer tissues by real-time RT-PCR.Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy.In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.Mitochondria are most notably involved in ATP production but also contribute to thermogenesis, free radical production, calcium homeostasis, and apoptosis [1]. ATP production is required for most cellular functions, and cellular energy requirements are largely met by the mitochondrial oxidative phosphorylation system. Mammalian mitochondria contain ~1000 proteins [2] but only 13 of them are encoded by the mitochondrial genome [3]. Other mitochondrial proteins are encoded by nuclear DNA, synthesized in the cytoplasm, and imported by the mitochondria.Although several mitochondrial proteins [4,5] form the nucleoid, which is a mitochondrial DNA-protein complex, their protective effects against mutagenesis are much less strong than those in the nuclear genome [6]. In addition, the high rate of mitochondrial DNA (mtDNA) mutation, which is several times higher than the rate for nuclear DNA [6-8], is likely explained by the production of reactive oxygen s