TP53 R282W point de perte partielle de fonction
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 | BIO-TP53-R282W |
|---|---|
| Type | Biomarqueur |
| Alias | TP53 R282W mutation partielle de la zone de perte de fonctionnementTP53 R282W — hotspot з частковою втратою функціїTP53 p.R282Wp53 R282W |
| État | reviewed 2026-04-27 | pending_clinical_signoff |
| Maladies | Aucune déclaration |
| Sources | SRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025 |
Données biomarqueurs
| Type de biomarqueur | gene_mutation |
|---|---|
| Détails de la mutation | {"exon": "8", "functional_impact": "partial loss_of_function (residual transactivation activity on some targets) + gain-of-function on others", "gene": "TP53", "gene_hugo_id": "11998", "hgvs_coding": "c.844C>T", "hgvs_protein": "p.R282W", "variant_type": "missense"} |
| Mesure | MéthodeTumor-tissue NGS panel (TP53 hotspot or full-gene); FFPE acceptable; ctDNA NGS for liquid biopsy Unitéscategorical (positive | negative); VAF % for clonality assessment |
| Biomarqueurs connexes | BIO-TP53-MUTATION BIO-TP53-R175H BIO-TP53-R248Q BIO-TP53-R273H |
Notes
R282 is the sixth most-mutated TP53 codon, often grouped with R248 and R273 as the canonical hotspot ring. Hybrid structural/contact mutant: R282 stabilizes the L1/S3 loop region adjacent to the DNA-binding surface, and R→W partially destabilizes the fold while altering contact geometry. Functional studies show R282W retains partial transactivation activity on a subset of canonical p53 targets (CDKN1A/p21, BBC3/PUMA at reduced levels) — termed "partial LoF" — while still gaining oncogenic activities. Clinically R282W behaves similarly to other hotspots: in AML/MDS poor chemo response → routes to venetoclax-azacitidine + alloSCT consideration; in CLL/MCL/MM high-risk regimen routing. Distinction from full LoF mutants (truncating, splice-site) may matter for emerging mutant-p53 reactivator drugs (eprenetapopt) where residual fold is required — R282W generally considered reactivatable in early-phase trials.
Utilisé par
Biomarqueur
BIO-TP53-R175H- TP53 R175H point de prise de fonctionBIO-TP53-R248Q- TP53 R248Q Hotspot de contact ADNBIO-TP53-R273H- TP53 R273H point de contact avec l'ADN