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Record W2606627097 · doi:10.1084/jem.20160894

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

2017· article· en· W2606627097 on OpenAlexaff
Andrea B. Moffitt, Sarah L. Ondrejka, Matthew McKinney, Rachel E. Rempel, John R. Goodlad, Chun Huat Teh, Sirpa Leppä, Susanna Mannisto, Panu E. Kovanen, Eric Tse, Rex Au-Yeung, Yok‐Lam Kwong, Gopesh Srivastava, Javeed Iqbal, Jiayu Yu, Kikkeri N. Naresh, Diego Villa, Randy D. Gascoyne, Jonathan Said, Magdalena Czader, Amy Chadburn, Kristy L. Richards, Deepthi Rajagopalan, Nicholas S. Davis, Eileen Smith, Brooke C. Palus, Tiffany J. Tzeng, Jane Healy, Patricia Lugar, Jyotishka Datta, Cassandra Love, Shawn Levy, David B. Dunson, Yuan Zhuang, Eric D. Hsi, Sandeep S. Davé

Bibliographic record

VenueThe Journal of Experimental Medicine · 2017
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of British ColumbiaBC Cancer Agency
FundersHertz FoundationNational Institutes of HealthNational Science Foundation
KeywordsKRASCancer researchLymphomaBiologyEnteropathyMutationT-cell lymphomaGeneticsGeneMedicineDiseaseImmunologyInternal medicine

Abstract

fetched live from OpenAlex

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1. We also identified mutations in KRAS, TP53, and TERT. Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

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)0.000
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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 head0.022
GPT teacher head0.307
Teacher spread0.285 · 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

Citations170
Published2017
Admission routes1
Has abstractyes

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