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Record W2187898585 · doi:10.1038/ncomms10013

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

2015· article· en· W2187898585 on OpenAlexafffund
Elizabeth J. Perlman, Samantha Gadd, Stefan T. Arold, Anand Radhakrishnan, Daniela S. Gerhard, Lawrence J. Jennings, Vicki Huff, Jaime M. Guidry Auvil, Tanja M. Davidsen, Jeffrey S. Dome, Daoud Meerzaman, Chih Hao Hsu, Cu Nguyen, James C. Anderson, Yussanne Ma, Andrew J. Mungall, Richard A. Moore, Marco A. Marra, Charles G. Mullighan, Jing Ma, David A. Wheeler, Oliver Hampton, Julie M. Gastier‐Foster, Nicole Ross, Malcolm A. Smith

Bibliographic record

VenueNature Communications · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRenal and related cancers
Canadian institutionsCanada's Michael Smith Genome Sciences Centre
FundersBC Cancer AgencyIDP FoundationKing Abdullah University of Science and TechnologyChildren’s Oncology GroupCanada's Michael Smith Genome Sciences CentreNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsWilms' tumorMutantHox geneMutationBiologyWilms tumourHistoneGeneCancer researchKidney developmentGeneticsPathologyGene expressionMedicineEmbryonic stem cell

Abstract

fetched live from OpenAlex

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

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: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.529
Threshold uncertainty score0.398

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 integrity0.0000.001
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 head0.019
GPT teacher head0.321
Teacher spread0.302 · 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 designNot applicable
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

Citations97
Published2015
Admission routes2
Has abstractyes

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