TP53 R175H point de prise 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-R175H |
|---|---|
| Type | Biomarqueur |
| Alias | TP53 R175H mutation de hotspot gain de fonctionTP53 R175H — hotspot з підсиленою функцієюTP53 p.R175Hp53 R175Hmutant structurel p53 |
| 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": "5", "functional_impact": "loss_of_function tumor suppressor + gain-of-function (mutant p53 gains pro-oncogenic activities including chemoresistance, migration, metabolic reprogramming)", "gene": "TP53", "gene_hugo_id": "11998", "hgvs_coding": "c.524G>A", "hgvs_protein": "p.R175H", "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-R248Q BIO-TP53-R273H BIO-TP53-R282W |
Notes
R175H is the most common TP53 missense hotspot across all human cancers (~5-7% of TP53-mutant tumors per IARC TP53 Database). Structural class mutant — the R175 substitution to histidine disrupts the DNA-binding domain fold (zinc-coordination region). Beyond loss-of-function (LoF), R175H is a canonical example of mutant-p53 GAIN-OF-FUNCTION (GOF): the mutant protein acquires pro-oncogenic activities (chemoresistance via NF-kB, increased migration/invasion, metabolic reprogramming, chronic inflammation). Clinical implication: R175H+ tumors generally have worse chemo response than TP53-WT or even other TP53-mut tumors. In AML: TP53-mut (any) including R175H → very poor outcomes with intensive chemo, route to alloSCT or venetoclax-azacitidine + clinical trials. In MM: routes to quadruplet per high-risk cytogenetics composite. Emerging GOF-targeting strategies (eprenetapopt/APR-246, arsenic trioxide for structural mutants) are largely investigational; R175H specifically among the reactivatable structural mutants.
Utilisé par
Biomarqueur
BIO-TP53-R248Q- TP53 R248Q Hotspot de contact ADNBIO-TP53-R273H- TP53 R273H point de contact avec l'ADNBIO-TP53-R282W- TP53 R282W point de perte partielle de fonctionnement