Mitochondrial DNA depletion may also have a role in pathogenesis of osteosarcoma

Abstract

We read the article by Yu et al. (2013a) entitled ‘Somatic mitochondrial DNA mutations in Chinese patients with Osteosarcoma’ with great interest. In this study, the aim of the authors was to investigate somatic mutations in mitochondrial DNA (mtDNA) and to explore their role in the pathogenesis and progression of osteosarcoma. With this aim the authors screened somatic mutations over the full-length mitochondrial genome of 31 osteosarcoma tumour tissue samples and corresponding peripheral blood samples from the same cohort of patients. They detected eleven somatic mutations in the mtDNA coding regions in their series. They indicated that nine of mtDNA mutations were missense or frameshift mutations that have the potential to hamper mitochondrial respiratory function. They concluded from their study that some missense and frameshift mutations are potentially harmful to proper mitochondrial activity and might play a vital role in osteosarcoma carcinogenesis. We share the authors' scientific view and think that this study is well constructed and scientific. However, we would like to express some constructive criticism. Osteosarcoma is a bone producing malignancy which mostly affects young adults. If there is early diagnosis, then it can be resectable, but it can also metastasise, usually to the lung (Caylak et al. 2006). There are previous studies investigating the presence and importance of mtDNA mutations in osteosarcoma (Guo et al. 2013). But, there are three major known alterations of mtDNA: (i) point mutations, (ii) large-scale deletions and (iii) mtDNA depletions (DiMauro & Bonilla 2004). Any one of these can be the cause of severe mitochondrial respiratory dysfunction, production of reactive oxygen species that are known to contribute in cancer development, and in turn may injure DNA further. For example, mitochondrial encephalomyopathy, lactic acidosis and stroke-like syndrome (MELAS) occur in association with a point mutation. On the other hand, Kearn–Sayre syndrome is caused by large-scale deletions. MtDNA depletion may also manifest as Alpers' syndrome. We understand that the authors have focused on point mutations in mtDNA only, but we feel that they should also cite studies in the literature which investigated mtDNA copy number in osteosarcoma (Yu et al. 2013b) and showed that changes in mtDNA copy number also occur in osteosarcoma. Thus, we feel that this well-written article would have benefited from mention that mtDNA variations other than point mutations may also have a role in the patho-carcinogenesis of osteosarcoma.