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Record W2888837017 · doi:10.1111/pcmr.12735

The tumor suppressor <scp>BAP</scp>1 cooperates with <scp>BRAFV</scp>600E to promote tumor formation in cutaneous melanoma

2018· article· en· W2888837017 on OpenAlexaff
Joshua D. Webster, Trang H. Pham, Xiumin Wu, Nicolas W. Hughes, Zhongwu Li, Klára Tótpál, Ho‐June Lee, Philamer Calses, Mira S. Chaurushiya, Eric Stawiski, Zora Modrušan, Matthew T. Chang, Christopher Tran, Wyne P. Lee, Sreedevi Chalasani, Jeffrey Hung, Neeraj Sharma, Sara M. Chan, Kathy Hötzel, Eric Talevich, A. Hunter Shain, Mengshu Xu, Jennie R. Lill, Vishva M. Dixit, Boris C. Bastian, Anwesha Dey

Bibliographic record

VenuePigment Cell & Melanoma Research · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsMicrosemi (Canada)Discovery Centre
FundersNational Cancer Institute
KeywordsBAP1MelanomaCancer researchSuppressorDeubiquitinating enzymeCancerBiologyNull cellUbiquitinCell cultureGeneGenetics

Abstract

fetched live from OpenAlex

Abstract The deubiquitinating enzyme BAP 1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAF V600E ) and UV to cause melanoma in mice, albeit at very low frequency. In addition, Bap1 ‐null melanoma cells derived from mouse tumors are more aggressive and colonize and grow at distant sites more than their wild‐type counterparts. Molecularly, Bap1 ‐null melanoma cell lines have increased DNA damage measured by γH2aX and hyperubiquitination of histone H2a. Therapeutically, these Bap1 ‐null tumors are completely responsive to BRAF ‐ and MEK ‐targeted therapies. Therefore, BAP 1 functions as a tumor suppressor and limits tumor progression in melanoma.

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)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.137
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.001

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 head0.021
GPT teacher head0.281
Teacher spread0.260 · 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.

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

Citations12
Published2018
Admission routes1
Has abstractyes

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