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Record W2034852369 · doi:10.1056/nejmoa1008433

<i>ARID1A</i> Mutations in Endometriosis-Associated Ovarian Carcinomas

2010· article· en· W2034852369 on OpenAlexafffundabout
Kimberly C. Wiegand, Sohrab P. Shah, Osama M. Al‐Agha, Yongjun Zhao, Kane Tse, Thomas Zeng, Janine Senz, Melissa K. McConechy, Michael S. Anglesio, Steve E. Kalloger, Winnie Yang, Alireza Heravi‐Moussavi, Ryan Giuliany, Christine Chow, John Fee, Abdalnasser Zayed, Leah Prentice, Nataliya Melnyk, Gulisa Turashvili, Allen Delaney, Jason Madore, Stephen Yip, Andrew McPherson, Gavin Ha, Lynda Bell, Sián Fereday, Angela Tam, Laura Galletta, Patricia N. Tonin, Diane Provencher, Dianne Miller, Steven J.M. Jones, Richard A. Moore, Gregg B. Morin, Arusha Oloumi, Niki Boyd, Samuel Aparício, Ie Ming Shih, Anne‐Marie Mes‐Masson, David D.L. Bowtell, Martin Hirst, C. Blake Gilks, Marco A. Marra, David G. Huntsman

Bibliographic record

VenueNew England Journal of Medicine · 2010
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChromatin Remodeling and Cancer
Canadian institutionsUniversité de MontréalHôpital Notre-DameMcGill University Health CentreCanada's Michael Smith Genome Sciences CentreCentre Hospitalier de l’Université de MontréalUniversity of British ColumbiaSimon Fraser UniversityBC Cancer Agency
FundersMedical Research and Materiel CommandNational Cancer InstituteNational Institutes of HealthCancer Council TasmaniaNational Health and Medical Research CouncilSanofiUniversity of British ColumbiaOvarian Cancer CanadaMichael Smith Health Research BCMedical Research CouncilCanadian Institutes of Health ResearchCanada's Michael Smith Genome Sciences CentreGenome Canada
KeywordsARID1AClear cell carcinomaClear cellCancer researchOvarian cancerSerous fluidEndometriosisCarcinomaMedicineSomatic cellTumor suppressor genePathologyBiologyMutationCancerCarcinogenesisInternal medicineGeneGenetics

Abstract

fetched live from OpenAlex

BACKGROUND: Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS: We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS: ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS: These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).

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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

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 integrity0.0000.000
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 head0.011
GPT teacher head0.261
Teacher spread0.251 · 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

Citations1,702
Published2010
Admission routes3
Has abstractyes

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