TP53 R175H ganancia de función
Vista determinista de la entidad fuente YAML. La autoridad clínica sigue con los ID de fuente citados y estado de firma del revisor.
| ID | BIO-TP53-R175H |
|---|---|
| Tipo | Biomarcador |
| Aliaces | TP53 R175H mutación del hotspot de ganancia de funciónTP53 R175H — hotspot з підсиленою функцієюTP53 p.R175Hp53 R175Hmutante estructural p53 |
| Situación | reviewed 2026-04-27 | pending_clinical_signoff |
| Enfermedades | Ninguna declarada |
| Fuentes | SRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025 |
Datos sobre biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalles de la mutación | {"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"} |
| Medición | MétodoPanel de NGS de tejido tumoral (punto de calor o gen completo de TP53); FFPE aceptable; NGs ctDNA para biopsia líquida Unidadescategorical (positive | negative); VAF % for clonality assessment |
| Productos químicos y químicos | BIO-TP53-MUTATION BIO-TP53-R248Q BIO-TP53-R273H BIO-TP53-R282W |
Notas
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.
Utilizado por
Biomarcador
BIO-TP53-R248Q- TP53 R248Q Punto de contacto con ADNBIO-TP53-R273H- Punto de contacto con ADN TP53 R273HBIO-TP53-R282W- TP53 R282W punto de pérdida parcial de la función