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TP53 R175H Hotspot für die Verstärkung der Funktion

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IDBIO-TP53-R175H
ArtBiomarker
Aliase
TP53 R175H Verstärkung der Funktion Hotspot-MutationTP53 R175H — hotspot з підсиленою функцієюTP53 p.R175Hp53 R175HStrukturelle p53 Mutante
Statusreviewed 2026-04-27 | pending_clinical_signoff
ErkrankungenNone declared
QuellenSRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025

Biomarker-Fakten

Biomarker-Typgene_mutation
Angaben zur 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"}
Messung
VerfahrenTumor-Gewebe NGS-Panel (TP53 Hotspot oder Vollgen); FFPE akzeptabel; ctDNA NGS für flüssige Biopsie
Einheitencategorical (positive | negative); VAF % for clonality assessment
Verwandte BiomarkerBIO-TP53-MUTATION BIO-TP53-R248Q BIO-TP53-R273H BIO-TP53-R282W

Anmerkungen

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.

Verwendet von

Biomarker