Les variantes génomiques bialléiques du MSH3 provoquent une polyposition associée au MSH3....
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| ID | BMA-MSH3-GERMLINE-POLYPOSIS-BIALLELIC |
|---|---|
| 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-MSH3-GERMLINE |
|---|---|
| Variante | MSH3 gérérale biallélique pathogène (polypose associée au MSH3) |
| Maladie | DIS-CRC |
| Niveau ESCAT | IIA |
| Combinaisons recommandées | colonoscopy q1-2y from age 25-30 with polypectomy (adenomas + serrated lesions), EGD q3-5y from age 30, endometrial sampling + TVUS in women per family-history risk profile, use NGS-based MSI assay or tetranucleotide-repeat assay if MSH3-deficiency suspected (standard MSI panels miss EMAST), partner-carrier reproductive counseling (autosomal-recessive) |
| Résumé des faits | MSH3 germline biallelic pathogenic variants cause MSH3-associated polyposis (Adam et al. 2016) — autosomal-recessive, attenuated adenomatous and serrated polyposis with elevated colorectal-cancer risk. Tumors show elevated microsatellite instability at di- and tetra-nucleotide repeats (EMAST — elevated microsatellite alterations at selected tetranucleotide repeats) rather than classical mono-/dinucleotide MSI-H, so standard MSI-H IHC and PCR panels may MISS MSH3-deficient tumors. Phenotype: CRC, gastroduodenal polyps, possibly other Lynch-spectrum tumors. Confirmed-carrier (biallelic) surveillance protocol follows attenuated polyposis / Lynch-like template: colonoscopy q1-2y from age 25-30 with polypectomy of all adenomas + serrated lesions, EGD q3-5y from age 30, consider endometrial sampling + TVUS in women per family-history context. Monoallelic (heterozygous) MSH3 carriers are not currently risk-elevated. ESCAT IIA. |
Notes
STUB — Wave A+B germline expansion. Linked Indication: IND-LYNCH-CARRIER- SURVEILLANCE used as closest-fit Lynch-like template (no MSH3-specific Indication exists yet). Two-Clinical-Co-Lead signoff queued. Critical: MSH3-deficient tumors exhibit EMAST not classical MSI-H — standard MSI assays may miss them; this matters both for predisposition diagnosis and for potential pembrolizumab eligibility in advanced disease. MSH3 syndrome is rare; published cohorts small (<25 families); penetrance estimates provisional.
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