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Record W3187516960 · doi:10.1016/j.devcel.2021.07.006

Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

2021· article· en· W3187516960 on OpenAlexfundno aff
Marica Rosaria Ippolito, Valentino Martis, Sara L. Martin, Andréa E. Tijhuis, Christy Hong, René Wardenaar, Marie Dumont, Johanna Zerbib, Diana C.J. Spierings, Daniele Fachinetti, Uri Ben‐David, Floris Foijer, Stefano Santaguida

Bibliographic record

VenueDevelopmental Cell · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrotubule and mitosis dynamics
Canadian institutionsnot available
FundersInstituto Mexicano del PetróleoAzrieli FoundationAssociazione Italiana per la Ricerca sul CancroKWF KankerbestrijdingMinistero dell’Istruzione, dell’Università e della RicercaHuman Frontier Science ProgramMinistero della SaluteFondazione CariploUniversità degli Studi di MilanoCentre National de la Recherche ScientifiqueCold Spring Harbor LaboratoryIstituto Europeo di OncologiaMassachusetts Institute of TechnologyCongressionally Directed Medical Research ProgramsUniversity of ManchesterIsrael Cancer AssociationUnited States - Israel Binational Science FoundationIsrael Cancer Research Fund
KeywordsBiologyAneuploidyChromosome instabilityGene dosageGeneGenome instabilityGeneticsChromosomeKaryotypeCancerCancer researchCopy-number variationMitosisGenomeDNA damageGene expressionDNA

Abstract

fetched live from OpenAlex

Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.008
GPT teacher head0.221
Teacher spread0.214 · 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 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

Citations197
Published2021
Admission routes1
Has abstractno

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