RT Journal Article SR Electronic T1 Mitochondrial DNA Copy Number Variation Across Human Cancers JF bioRxiv FD Cold Spring Harbor Laboratory SP 021535 DO 10.1101/021535 A1 Ed Reznik A1 Martin L. Miller A1 Yasin Senbabaoglu A1 Nadeem Riaz A1 William Lee A1 Chris Sander YR 2015 UL http://biorxiv.org/content/early/2015/06/27/021535.abstract AB In cancer, mitochondrial dysfunction, through mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), contributes to the malignant transformation and progress of tumors. Here, we report the first large-scale survey of mtDNA copy number variation across 21 distinct solid tumor types, examining over 13,000 tissue samples profiled with next-generation sequencing methods. We find a tendency for cancers, especially of the bladder and kidney, to be significantly depleted of mtDNA, relative to matched normal tissue. We show that mtDNA copy number is correlated to the expression of mitochondrially-localized metabolic pathways, suggesting that mtDNA copy number variation reflect gross changes in mitochondrial metabolic activity. Finally, we identify a subset of tumor-type-specific somatic alterations, including IDH1 and NF1 mutations in gliomas, whose incidence is strongly correlated to mtDNA copy number. Our findings suggest that modulation of mtDNA copy number may play a role in the pathology of cancer.