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Record W4413431855 · doi:10.1002/path.6466

<scp><i>APC</i></scp>‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive <scp>WNT</scp> activation

2025· article· en· W4413431855 on OpenAlexafffund
Fiona Chan‐Pak‐Choon, Catherine Beaumont, José Camacho Valenzuela, Josianne Leblanc, Sonja Dahlum, Reiner Siebert, François Thuot, Marc Pusztaszeri, Jacinthe Chênevert, Paz Polak, Tania Cruz Mariño, Bárbara Rivera, William D. Foulkes

Bibliographic record

VenueThe Journal of Pathology · 2025
Typearticle
Languageen
FieldMedicine
TopicGenetic factors in colorectal cancer
Canadian institutionsMcGill University Health CentreHôtel-Dieu de QuébecMcGill UniversityCentre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-JeanUniversité LavalJewish General Hospital
FundersInstituto de Salud Carlos IIICanadian Institutes of Health ResearchMerck CanadaGlaxoSmithKlinePfizerInstitut de recherche, Centre universitaire de santé McGill
KeywordsTranscriptomeWnt signaling pathwaySalivary glandCell biologyBiologyMedicinePathologySignal transductionGeneticsGene expressionGene

Abstract

fetched live from OpenAlex

Attenuated familial adenomatous polyposis (AFAP) is a disorder caused by germline pathogenic variants in APC and is characterized by the presence of <100 colonic polyps and a high lifetime risk of developing colorectal cancer. Salivary gland basal cell tumours are uncommon and have not previously been reported in AFAP. We present a family with AFAP and multiple salivary gland tumours, including basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC). The colon and salivary gland tumours showed abnormal nuclear β-catenin staining. Genomic analysis of both parotid BCACs showed copy-number-neutral loss of heterozygosity (CNN-LOH) at the APC locus, implicating loss of full-length APC in the aetiology of parotid BCACs. In contrast, the submandibular BCAC showed a p.(Ile35Thr) CTNNB1 mutation. Spatial transcriptomic analysis revealed a stepwise increase in the expression of WNT pathway genes across the proband's salivary lesions, from benign (intercalated duct hyperplasia and BCAs) to malignant (BCACs). Our results showcase BCA and BCAC as potential new phenotypes of AFAP. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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)0.003
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 score0.624
Threshold uncertainty score0.785

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.014
GPT teacher head0.284
Teacher spread0.269 · 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

Citations1
Published2025
Admission routes2
Has abstractyes

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