Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, ICGC Breast Cancer Working Group

Research output: Contribution to journalArticle

Abstract

Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.

Original languageEnglish (US)
Pages (from-to)814-824
Number of pages11
JournalGenome Research
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Nuclear Fusion
Human Genome
Mitochondrial DNA
Mitochondrial Genome
Neoplasms
Genome
Architectural Accessibility
Double-Stranded DNA Breaks
Nuclear Envelope
Mitochondrial Membranes
Base Pairing
Cell Cycle
Cytoplasm
DNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, & ICGC Breast Cancer Working Group (2015). Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Research, 25(6), 814-824. https://doi.org/10.1101/gr.190470.115

Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. / ICGC Prostate Cancer Working Group; ICGC Bone Cancer Working Group; ICGC Breast Cancer Working Group.

In: Genome Research, Vol. 25, No. 6, 01.06.2015, p. 814-824.

Research output: Contribution to journalArticle

ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group & ICGC Breast Cancer Working Group 2015, 'Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells', Genome Research, vol. 25, no. 6, pp. 814-824. https://doi.org/10.1101/gr.190470.115
ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, ICGC Breast Cancer Working Group. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Research. 2015 Jun 1;25(6):814-824. https://doi.org/10.1101/gr.190470.115
ICGC Prostate Cancer Working Group ; ICGC Bone Cancer Working Group ; ICGC Breast Cancer Working Group. / Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. In: Genome Research. 2015 ; Vol. 25, No. 6. pp. 814-824.
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abstract = "Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.",
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AU - Mifsud, William

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AU - Caldas, Carlos

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AU - Tan, Benita K T

AU - Aparicio, Samuel

AU - Span, Paul N.

AU - Martens, John W M

AU - Knappskog, Stian

AU - Vincent-Salomon, Anne

AU - Børresen-Dale, Anne Lise

AU - Eyfjörd, Jórunn Erla

AU - Flanagan, Adrienne M.

AU - Foster, Christopher

AU - Neal, David E.

AU - Cooper, Colin

AU - Eeles, Rosalind

AU - Lakhani, Sunil R.

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