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Record W2014323284 · doi:10.1038/ncomms4644

Processed pseudogenes acquired somatically during cancer development

2014· article· en· W2014323284 on OpenAlexafffund
Susanna L. Cooke, Adam Shlien, John L. Marshall, Christodoulos Pipinikas, Sancha Martin, José M. C. Tubío, Yilong Li, Andrew Menzies, Laura Mudie, Manasa Ramakrishna, Lucy Yates, Helen Davies, Niccolò Bolli, Graham R. Bignell, Patrick Tarpey, Sam Behjati, Serena Nik‐Zainal, Elli Papaemmanuil, Vitor H. Teixeira, Keiran Raine, Sarah O’Meara, Maryam S. Dodoran, Jon W. Teague, Adam P. Butler, Christine A. Iacobuzio–Donahue, Thomas Santarius, Richard G. Grundy, David Malkin, Mel Greaves, Nikhil C. Munshi, Adrienne M. Flanagan, David D.L. Bowtell, Denis Larsimont, Jorge S. Reis‐Filho, Alex Boussioutas, Jack A. Taylor, Neil Hayes, Sam M. Janes, P. Andrew Futreal, Michael R. Stratton, Ultan McDermott, Peter J. Campbell, Elena Provenzano, Marc J. van de Vijver, Andrea L. Richardson, Colin A. Purdie, Sarah E. Pinder, Gaëtan Mac Grogan, Anne Vincent‐Salomon, Dorthe Grabau, Torill Sauer, Øystein Garred, Anna Ehinger, Gert G. Van den Eynden, Carolien H. M. van Deurzen, Roberto Salgado, Jane E. Brock, Sunil R. Lakhani, Dilip D. Giri, Laurent Arnould, Jocelyne Jacquemier, Isabelle Treilleux, Carlos Caldas, Suet‐Feung Chin, Aquila Fatima, Alastair M. Thompson, Alasdair Stenhouse, John A. Foekens, John W.M. Martens, Anieta M. Sieuwerts, Arjen Brinkman, Henk G. Stunnenberg, Paul N. Span, Fred C.G.J. Sweep, Christine Desmedt, Christos Sotiriou, Gilles Thomas, Annegein Broeks, Anita Langerød, Samuel Aparício, Peter T. Simpson, Laura van ‘t Veer, Jórunn E. Eyfjörd, Hólmfríður Hilmarsdóttir, Jón G. Jónasson, Anne‐Lise Børresen‐Dale, Ming Ta Michael Lee, Bernice H. Wong, Benita Kiat Tee Tan, Gerrit K. Hooijer

Bibliographic record

VenueNature Communications · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsSickKids FoundationHospital for Sick ChildrenBC Cancer AgencyUniversity of Toronto
FundersNational Research Council CanadaRosetrees TrustUniversity College London Hospitals NHS Foundation TrustEuropean CommissionWellcome TrustAcademy of Medical SciencesKay Kendall Leukaemia FundNational Institute for Health and Care ResearchNational Cancer InstituteNational Institutes of HealthCancer Research UK
KeywordsPseudogeneBiologyRetrotransposonGeneticsGermlineGeneGermline mutationExonIntronContext (archaeology)MutationSomatic cellCancerGenomeTransposable element

Abstract

fetched live from OpenAlex

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.521
Threshold uncertainty score0.412

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.012
GPT teacher head0.282
Teacher spread0.270 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations112
Published2014
Admission routes2
Has abstractyes

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