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Record W2169123048 · doi:10.1101/gr.190470.115

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

2015· article· en· W2169123048 on OpenAlexaff
Young Seok Ju, José M. C. Tubío, William Mifsud, Beiyuan Fu, Helen Davies, Manasa Ramakrishna, Yilong Li, Lucy Yates, Gunes Gundem, Patrick Tarpey, Sam Behjati, Elli Papaemmanuil, Sancha Martin, Anthony Fullam, Moritz Gerstung, Jyoti Nangalia, Anthony R. Green, Carlos Caldas, Åke Borg, Andrew Tutt, Ming Ta Michael Lee, Laura J. van’t Veer, Benita Kiat Tee Tan, Samuel Aparício, Paul N. Span, John W.M. Martens, Stian Knappskog, Anne Vincent‐Salomon, Anne‐Lise Børresen‐Dale, Jórunn E. Eyfjörd, Ola Myklebost, Adrienne M. Flanagan, Christopher S. Foster, David E. Neal, Colin Cooper, Rosalind A. Eeles, G. Steven Bova, Sunil R. Lakhani, Christine Desmedt, Andrea L. Richardson, Colin A. Purdie, Alastair M. Thompson, Ultan McDermott, Fengtang Yang, Serena Nik-Zainal, Peter J. Campbell, Michael R. Stratton

Bibliographic record

VenueGenome Research · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsBC Cancer Agency
FundersBiotechnology and Biological Sciences Research CouncilNational Institute for Health and Care ResearchUniversity College London Hospitals NHS Foundation TrustEuropean CommissionRoyal Marsden NHS Foundation TrustFP7 People: Marie-Curie ActionsCancer Research UKWellcome TrustWellcomeEuropean Molecular Biology Organization
KeywordsBiologyMitochondrial DNAGenomeSomatic cellNuclear DNAGeneticsNuclear genemitochondrial fusionDNA repairHeavy strandMolecular biologyMitochondrionDNACell biologyGeneTransfer RNARNA

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.070
GPT teacher head0.347
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations173
Published2015
Admission routes1
Has abstractyes

Explore more

Same venueGenome ResearchSame topicMitochondrial Function and PathologyFrench-language works237,207