title: Mitochondrial DNA copy number variation across human cancers.
abstract: 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.
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Ed
authors.identifier: http://orcid.org/0000-0002-6511-5947
authors.initials: E
authors.lastname: Reznik
authors.affiliation: Cancer Research UK, Cambridge Institute, Cambridge, United Kingdom.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Miller
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Yasin
authors.identifier: http://orcid.org/0000-0003-0958-958X
authors.initials: Y
authors.lastname: Şenbabaoğlu
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Riaz
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Judy
authors.initials: J
authors.lastname: Sarungbam
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Hikmat A
authors.initials: HA
authors.lastname: Al-Ahmadie
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.|Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
mesh_terms: D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009369:Neoplasms / Q000473:pathology*; D057089:Pathology, Molecular
chemical_list: D004272:DNA, Mitochondrial
keywords: cancer; computational biology; copy number; human; human biology; medicine; metabolism; mitochondria; mtDNA; sequencing; systems biology