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Record W2781715103 · doi:10.1038/s41467-018-05914-x

The prognostic effects of somatic mutations in ER-positive breast cancer

2018· article· en· W2781715103 on OpenAlexafffund
Obi L. Griffith, Nicholas C. Spies, Meenakshi Anurag, Malachi Griffith, Jingqin Luo, Dongsheng Tu, Belinda Yeo, Jason Kunisaki, Christopher A. Miller, Kilannin Krysiak, Jasreet Hundal, Benjamin J. Ainscough, Zachary L. Skidmore, Katie M. Campbell, Runjun D. Kumar, Catrina C. Fronick, Lisa Cook, Jacqueline Snider, Sherri R. Davies, Shyam M. Kavuri, Eric C. Chang, Vincent Magrini, David E. Larson, Robert S. Fulton, Shuzhen Liu, Samuel Leung, David Voduc, Ron Bose, Mitch Dowsett, Richard K. Wilson, Torsten O. Nielsen, Elaine R. Mardis, Matthew J. Ellis

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsUniversity of British Columbia
FundersNational Cancer InstituteNational Institute for Health and Care ResearchCanadian Cancer Society Research InstituteNational Human Genome Research InstituteSusan G. KomenCancer Prevention and Research Institute of TexasU.S. Department of Defense
KeywordsBreast cancerSomatic cellGermline mutationOncologyMedicineMutationInternal medicineNonsense mutationCancer researchCancerGeneBioinformaticsGeneticsBiologyMissense mutation

Abstract

fetched live from OpenAlex

Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.558
Threshold uncertainty score0.295

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 science0.0000.000
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 head0.005
GPT teacher head0.283
Teacher spread0.278 · 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 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

Citations143
Published2018
Admission routes2
Has abstractyes

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