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Record W4393223713 · doi:10.1038/s41525-024-00405-z

Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib

2024· article· en· W4393223713 on OpenAlexafffund
Katrina M. Ingley, Matthew Zatzman, Adam M. Fontebasso, Winnie Lo, Vallijah Subasri, Anna Goldenberg, Yujiao Li, Scott Davidson, Neena Kanwar, Larissa Waldman, Ledia Brunga, Yael Babichev, Elizabeth G. Demicco, Abha A. Gupta, Marta Szybowska, Seng Thipphavong, David Malkin, Anita Villani, Adam Shlien, Rebecca A. Gladdy, Raymond H. Kim

Bibliographic record

Venuenpj Genomic Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicGastrointestinal Tumor Research and Treatment
Canadian institutionsUniversity Health NetworkUniversity of TorontoSinai Health SystemPrincess Margaret Cancer CentreHospital for Sick Children
FundersGarron Family Cancer CentreHospital for Sick ChildrenPrincess Margaret Cancer Foundation
KeywordsGiSTImatinibProbandExonGermlineStromal tumorGermline mutationGeneticsBiologyCancer researchCarcinogenesisMedicineGeneMutationStromal cell

Abstract

fetched live from OpenAlex

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

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)0.001
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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.941
Threshold uncertainty score0.496

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.045
GPT teacher head0.370
Teacher spread0.325 · 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 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
Published2024
Admission routes2
Has abstractyes

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