POLD1 variantes pathogènes germaines dans le domaine de l'exonucléase (lecture d'épreuve) causent PPAP —...
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | BMA-POLD1-GERMLINE-POLYMERASE-PROOFREADING |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-CRC |
| Sources | SRC-NCCN-GENETIC-FAMILIAL-CRC-2025 |
Faits relatifs à l ' action en justice
| Biomarqueur | BIO-POLD1-GERMLINE |
|---|---|
| Variante | POLD1 exonucléase-domaine pathogène (PPAP — polyposition associée à la correction d'épreuves de polymérase) |
| Maladie | DIS-CRC |
| Niveau ESCAT | IIA |
| Combinaisons recommandées | colonoscopy q1-2y starting age 20-25 with polypectomy, endometrial sampling + TVUS q1-2y from age 30-35 (women); consider earlier given higher endometrial risk vs POLE, discussion of risk-reducing hysterectomy + BSO after childbearing (INTENSIFIED-track conversation), EGD q3y from age 30, annual urinalysis from age 30, for POLD1-mutant advanced disease: pembrolizumab 200 mg q3w — high response rate in TMB-H ultramutator setting |
| Résumé des faits | POLD1 germline pathogenic variants in the exonuclease (proofreading) domain cause PPAP — similar to POLE-PPAP but with a stronger endometrial-cancer signal in women (lifetime endometrial risk ~50% per published cohorts). Phenotype includes attenuated polyposis with early-onset CRC, endometrial cancer, and CNS tumors in some families. Confirmed-carrier surveillance protocol (Lynch-like): colonoscopy q1-2y starting age 20-25, endometrial sampling + TVUS q1-2y from age 30-35 in women (consider earlier given higher endometrial risk than POLE), EGD q3y from age 30, urinalysis q1y from age 30. Tumor ultramutator phenotype (TMB high) suggests immunotherapy responsiveness in advanced disease; pembrolizumab FDA- approved for TMB-H solid tumors. Risk-reducing hysterectomy + BSO after childbearing is reasonable to discuss in POLD1 carriers (analogous to Lynch INTENSIFIED-track decision). ESCAT IIA. |
Notes
STUB — Wave A+B germline expansion. Linked Indication: IND-LYNCH-CARRIER- SURVEILLANCE used as closest-fit; no POLD1-specific Indication exists. Two-Clinical-Co-Lead signoff queued. Variant classification: only exonuclease-domain variants (Ser478Asn, Pro327Leu, Leu474Pro most common) drive PPAP. Endometrial-cancer risk in POLD1 carriers appears higher than POLE — supports earlier / denser endometrial surveillance + low-threshold risk-reducing surgery discussion at completion of childbearing.
Utilisé par
No reverse references found in the YAML corpus.