TY - JOUR
T1 - Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells
AU - ICGC Bone Cancer Working Group
AU - ICGC Breast Cancer Working Group
AU - ICGC Prostate Cancer Working Group
AU - Ju, Young Seok
AU - Tubio, Jose M.C.
AU - Mifsud, William
AU - Fu, Beiyuan
AU - Davies, Helen R.
AU - Ramakrishna, Manasa
AU - Li, Yilong
AU - Yates, Lucy
AU - Gundem, Gunes
AU - Tarpey, Patrick S.
AU - Behjati, Sam
AU - Papaemmanuil, Elli
AU - Martin, Sancha
AU - Fullam, Anthony
AU - Gerstung, Moritz
AU - Nangalia, Jyoti
AU - Green, Anthony R.
AU - Caldas, Carlos
AU - Borg, Åke
AU - Tutt, Andrew
AU - Michael Lee, Ming Ta
AU - Van'T Veer, Laura J.
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.
AU - Desmedt, Christine
AU - Thomas, Gilles
AU - Richardson, Andrea L.
AU - Purdie, Colin A.
AU - Thompson, Alastair M.
AU - McDermott, Ultan
AU - Yang, Fengtang
AU - Nik-Zainal, Serena
AU - Campbell, Peter J.
AU - Stratton, Michael R.
N1 - Publisher Copyright:
© 2015 Ju et al.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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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U2 - 10.1101/gr.190470.115
DO - 10.1101/gr.190470.115
M3 - Article
C2 - 25963125
AN - SCOPUS:84931830812
SN - 1088-9051
VL - 25
SP - 814
EP - 824
JO - Genome research
JF - Genome research
IS - 6
ER -