Mitochondrial DNA copy number variation across human cancers

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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere10769
JournaleLife
Volume5
Issue numberFEBRUARY2016
DOIs
StatePublished - Feb 22 2016
Externally publishedYes

Fingerprint

DNA Copy Number Variations
Mitochondrial DNA
Neoplasms
Tumors
Genes
cdc Genes
Atlases
Sequence Deletion
Urinary Bladder Neoplasms
Glioma
Breast
Cells
Genome
Tissue
Kidney
Gene Expression
Mutation
Incidence

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Reznik, E., Miller, M. L., Şenbabaoğlu, Y., Riaz, N., Sarungbam, J., Tickoo, S. K., ... Sander, C. (2016). Mitochondrial DNA copy number variation across human cancers. eLife, 5(FEBRUARY2016), [e10769]. https://doi.org/10.7554/eLife.10769

Mitochondrial DNA copy number variation across human cancers. / Reznik, Ed; Miller, Martin L.; Şenbabaoğlu, Yasin; Riaz, Nadeem; Sarungbam, Judy; Tickoo, Satish K.; Al-Ahmadie, Hikmat A.; Lee, William; Seshan, Venkatraman E.; Hakimi, A. Ari; Sander, Chris.

In: eLife, Vol. 5, No. FEBRUARY2016, e10769, 22.02.2016.

Research output: Contribution to journalArticle

Reznik, E, Miller, ML, Şenbabaoğlu, Y, Riaz, N, Sarungbam, J, Tickoo, SK, Al-Ahmadie, HA, Lee, W, Seshan, VE, Hakimi, AA & Sander, C 2016, 'Mitochondrial DNA copy number variation across human cancers', eLife, vol. 5, no. FEBRUARY2016, e10769. https://doi.org/10.7554/eLife.10769
Reznik E, Miller ML, Şenbabaoğlu Y, Riaz N, Sarungbam J, Tickoo SK et al. Mitochondrial DNA copy number variation across human cancers. eLife. 2016 Feb 22;5(FEBRUARY2016). e10769. https://doi.org/10.7554/eLife.10769
Reznik, Ed ; Miller, Martin L. ; Şenbabaoğlu, Yasin ; Riaz, Nadeem ; Sarungbam, Judy ; Tickoo, Satish K. ; Al-Ahmadie, Hikmat A. ; Lee, William ; Seshan, Venkatraman E. ; Hakimi, A. Ari ; Sander, Chris. / Mitochondrial DNA copy number variation across human cancers. In: eLife. 2016 ; Vol. 5, No. FEBRUARY2016.
@article{51fb88506e6247a4978bd19ca6f8379f,
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.",
author = "Ed Reznik and Miller, {Martin L.} and Yasin Şenbabaoğlu and Nadeem Riaz and Judy Sarungbam and Tickoo, {Satish K.} and Al-Ahmadie, {Hikmat A.} and William Lee and Seshan, {Venkatraman E.} and Hakimi, {A. Ari} and Chris Sander",
year = "2016",
month = "2",
day = "22",
doi = "10.7554/eLife.10769",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "FEBRUARY2016",

}

TY - JOUR

T1 - Mitochondrial DNA copy number variation across human cancers

AU - Reznik, Ed

AU - Miller, Martin L.

AU - Şenbabaoğlu, Yasin

AU - Riaz, Nadeem

AU - Sarungbam, Judy

AU - Tickoo, Satish K.

AU - Al-Ahmadie, Hikmat A.

AU - Lee, William

AU - Seshan, Venkatraman E.

AU - Hakimi, A. Ari

AU - Sander, Chris

PY - 2016/2/22

Y1 - 2016/2/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84961279532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961279532&partnerID=8YFLogxK

U2 - 10.7554/eLife.10769

DO - 10.7554/eLife.10769

M3 - Article

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - FEBRUARY2016

M1 - e10769

ER -