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Record W4417304993 · doi:10.1038/s41467-025-66428-x

Early genetic evolution of driver mutations in uveal melanoma

2025· article· en· W4417304993 on OpenAlexaff
James J. Dollar, Christina L. Decatur, Ezekiel Weis, Amy C Schefler, Miguel A. Materin, Timothy Fuller, Alison H. Skalet, David A. Reichstein, Ivana K. Kim, Kisha Piggott, Hakan Demirci, Thomas Aaberg, Prithvi Mruthyunjaya, Basil K. Williams, Eugene Shildkrot, Scott C. N. Oliver, Devron H. Char, Antonio Capone, John O. Mason, Scott D. Walter, Michael M. Altaweel, Jill R. Wells, Dan S. Gombos, Jay S. Duker, Peter Hovland, Tony Tsai, Cameron Javid, Michael Durante, Kyle R. Covington, Song Zhang, Zélia M. Corrêa, J. William Harbour

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldMedicine
TopicOcular Oncology and Treatments
Canadian institutionsUniversity of CalgaryUniversity of Alberta
FundersNational Institute of General Medical SciencesNational Cancer InstituteNational Eye InstituteSylvester Comprehensive Cancer Center, University of Miami Health SystemsUniversity of MiamiCastle BiosciencesResearch to Prevent Blindness
KeywordsMelanomaMalignant transformationGNAQMicrometastasisSubclinical infectionGene deletionSomatic evolution in cancerCancer

Abstract

fetched live from OpenAlex

Uveal melanoma (UM) is an aggressive eye cancer that frequently results in metastatic death despite successful primary tumor treatment. Subclinical micrometastasis is thought to occur early, when tumors are small and difficult to distinguish from benign nevi. However, the early genetic evolution of UM is poorly understood, and biomarkers for malignant transformation are lacking. Here, we perform integrated genetic profiling of 1140 primary UMs, including 131 small tumors. A clinically available 15-gene expression profile (15-GEP) prospectively validated by our group is more accurate than driver mutations for predicting patient survival. Small tumors are significantly more likely to be in earlier stages of genetic evolution than larger tumors. Further, the 15-GEP support vector machine discriminant score predicts small tumors undergoing transformation from low-risk Class 1 to high-risk Class 2 profile. These results shed light on the early genetic evolution of UM and move us closer to a molecular definition of malignant transformation in this cancer type.

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 score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
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 head0.322
Teacher spread0.311 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

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