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Record W4415453358 · doi:10.1210/jendso/bvaf149.2485

SUN-283 Impact of Chompret Criteria on the Diagnosis of with Li-Fraumeni Syndrome: Frequency of the TP53 Germline Pathogenic Variant (p.R337H) inTertiary Centers in Brazil

2025· article· en· W4415453358 on OpenAlexaff
Mariana Braga Lacerda, Marina Buchpiguel, Luiza Neme Pimentel, Luiz Antonio Senna Leite, Madson Q. Almeida, Mariana Ferreira de Assis Funari, Ana Cláudia Latronico, Ana O. Hoff, Berenice B. Mendonça, Maria Del Pilar Estevez-Diz, Maria Candida Barisson Villares Fragoso

Bibliographic record

VenueJournal of the Endocrine Society · 2025
Typearticle
Languageen
FieldMedicine
TopicCancer-related Molecular Pathways
Canadian institutionsWiLAN (Canada)
Fundersnot available
KeywordsGermlineBreast cancerCancerGermline mutationAdrenocortical carcinomaAge of onsetCarcinomaIndex case

Abstract

fetched live from OpenAlex

Abstract Disclosure: M.B. Lacerda: None. M. Buchpiguel: None. M. Sousa: None. L. Pimentel: None. L. Leite: None. M.Q. Almeida: None. M. Ferreira: None. M.F. Funari: None. A. Latronico: None. A.O. Hoff: None. B.B. Mendonca: None. M. Diz: None. M. Fragoso: None. Introduction: Li-Fraumeni Syndrome (LFS) is an autosomal dominant hereditary condition caused by pathogenic variants (PVs) in the TP53, which predisposes individuals to early-onset tumors. The germline p.R337H variant is particularly prevalent in Brazil, especially in the South and Southeast regions. Diagnosis is based on the Chompret Criteria {(1. An individual with a tumor belonging to the LFS spectrum before the age of 46 AND At least one first- or second-degree relative with a tumor associated with LFS (except breast cancer if the index case had breast cancer) before the age of 56 OR with multiple tumors OR 2. An individual with multiple tumors (except breast), two of which belong to the LFS spectrum, and the first of them occurred before the age of 46 OR 3. An individual with adrenocortical carcinoma or choroid plexus tumor, regardless of family history.)}. This study evaluates the application of these criteria in LFS. Objective: to analyze clinical and diagnostic data related to TP53 p.R337H variant both retrospectively and prospectively. The secondary objective was to assess the effectiveness of the Chompret Criteria in identifying individuals at increased risk of developing LFS. Subjects and Methods: This study included patients treated at tertiary centers between 2002 and 2024 who met the Chompret Criteria and underwent TP53 gene sequencing. Clinical, epidemiological, and laboratory data were obtained. The study was approved by the local Ethics Committee, and informed consent was obtained. Results: A total of 381 index cases were analyzed. Among these, 107 cases (28%) had TP53 PV, with 77 (72%) identified as carriers of the p.R337H variant. The distribution of Chompret Criteria among p.R337H carriers was as follows: Criterion 1 (25.97%), Criterion 2 (7.79%), and Criterion 3 (66.23%), being the most effective for screening. Carriers of the p.R337H PV were predominantly female (77%), with a mean age of 33 years at diagnosis, and were predominantly from the Southeast region (95%), particularly from the states of São Paulo (79.22%) and Minas Gerais (15.6%). Among p.R337H carriers, the primary tumor sites were adrenal gland (63.52%), breast (23.52%), and soft tissues (7.05%). The most frequent histopathological diagnoses were pediatric adrenal tumors (41.2%), adrenocortical carcinoma (21.2%), and invasive ductal carcinoma of the breast (15.3%). The mortality rate among carriers was 29.9%. Discussion/Conclusion: The Chompret Criteria, particularly Criterion 3, proved highly effective in identifying patients carrying the p.R337H variant. The high prevalence of the p.R337H PV among patients from Southeast Brazil, associated with primary tumors, highlights the need for effective surveillance strategies and early diagnosis, supporting genetic screening in at-risk populations. Presentation: Sunday, July 13, 2025

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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 score0.444
Threshold uncertainty score0.474

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.009
GPT teacher head0.287
Teacher spread0.278 · 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".

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Citations0
Published2025
Admission routes1
Has abstractyes

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