Mitochondrial DNA copy number variation across human cancers

Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project.

We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti-correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities.

eLife. 2016 Feb 22*** epublish ***

Ed Reznik, Martin L Miller, Yasin Şenbabaoğlu, Nadeem Riaz, Judy Sarungbam, Satish K Tickoo, Hikmat A Al-Ahmadie, William Lee, Venkatraman E Seshan, A Ari Hakimi, Chris Sander

Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States., Cancer Research UK, Cambridge Institute, Cambridge, United Kingdom., Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States., Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States., Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States., Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States., Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.

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