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Record W2591837371 · doi:10.1158/0008-5472.can-16-2179

Recommended Guidelines for Validation, Quality Control, and Reporting of <i>TP53</i> Variants in Clinical Practice

2017· review· en· W2591837371 on OpenAlexaff
Bernard Leroy, Mandy L. Ballinger, Fanny Baran‐Marszak, Gareth L. Bond, Antony W. Braithwaite, Nicole Concin, Lawrence A. Donehower, Wafik S. El‐Deiry, Pierre Fenaux, Gianluca Gaïdano, Anita Langerød, Eva Hellstrom-Lindberg, Richard Iggo, Jacqueline Lehmann‐Che, David Malkin, Ute M. Moll, Jeffrey N. Myers, Kim E. Nichols, Šárka Pospı́šilová, Patrícia Ashton‐Prolla, Davide Rossi, Sharon A. Savage, Louise C. Strong, Patricia N. Tonin, Robert Zeillinger, Thorsten Zenz, Joseph F. Fraumeni, Peter E.M. Taschner, Pierre Hainaut, Thierry Soussi

Bibliographic record

VenueCancer Research · 2017
Typereview
Languageen
FieldMedicine
TopicCancer-related Molecular Pathways
Canadian institutionsMcGill University Health CentreCanada Research ChairsHospital for Sick ChildrenUniversity of Toronto
FundersNational Institutes of Health
KeywordsContext (archaeology)GermlineCancerExonIntronGene nomenclatureRNA splicingGeneClinical PracticeGeneticsGermline mutationMedicineBiologyBioinformaticsComputational biologyMutationFamily medicineNomenclatureRNA

Abstract

fetched live from OpenAlex

Abstract Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li–Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250–60. ©2017 AACR.

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)0.043
metaresearch head score (Gemma)0.238
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesMetaresearch
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.964
Threshold uncertainty score0.985

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0430.238
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.002
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 head0.835
GPT teacher head0.718
Teacher spread0.116 · 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; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreReview

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

Citations94
Published2017
Admission routes1
Has abstractyes

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