TP53 R175H ganho de função
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| ID | BIO-TP53-R175H |
|---|---|
| Tipo | Biomarcador |
| Alegais | TP53 R175H mutação do hotspot de ganho de funçãoTP53 R175H — hotspot з підсиленою функцієюTP53 p.R175Hp53 R175Hmutante estrutural p53 |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff |
| Doenças | Nenhuma declaração |
| Fontes | SRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"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"} |
| Medição | MétodoTumor-tissue NGS panel (TP53 hotspot or full-gene); FFPE acceptable; ctDNA NGS for liquid biopsy Unidadescategorical (positive | negative); VAF % for clonality assessment |
| Biomarcadores relacionados | 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.
Usado por
Biomarcador
BIO-TP53-R248Q- TP53 R248Q Hotspot de contato com DNABIO-TP53-R273H- TP53 R273H ponto de contacto com ADNBIO-TP53-R282W- TP53 R282W ponto de perda parcial de função