TP53 R248Q Point de contact avec l'ADN
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-R248Q |
|---|---|
| Type | Biomarqueur |
| Alias | Mutant à contact ADNTP53 R248Q mutation des hotspots à contact avec l'ADNTP53 R248Q — hotspot ДНК-контактуTP53 p.R248Qp53 R248Q |
| 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": "7", "functional_impact": "loss_of_function (DNA-contact residue lost) + gain-of-function (mutant p53 gains pro-oncogenic activities)", "gene": "TP53", "gene_hugo_id": "11998", "hgvs_coding": "c.743G>A", "hgvs_protein": "p.R248Q", "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-R273H BIO-TP53-R282W |
Notes
R248 is one of the six most-mutated codons in TP53 (along with R175, G245, R249, R273, R282). DNA-contact class: R248 sits in the L3 loop and makes direct base-specific contact with the DNA minor groove. Substitution to glutamine (R248Q) abolishes sequence-specific DNA binding while preserving overall fold (distinguishing it from structural R175H). R248Q has well-documented gain-of-function (GOF) activities in mouse models — accelerates tumorigenesis and metastasis beyond simple p53-null. Clinical implications mirror other TP53 hotspots: in AML/MDS routes away from intensive chemo toward venetoclax-azacitidine + alloSCT; in CLL/MCL/MM contraindicates chemoimmuno or routes to high-risk-cytogenetics regimens. Distinction from R248W (different substitution, also a hotspot) — R248Q tends to retain partial folding while R248W more disruptive; both are pathogenic.
Utilisé par
Biomarqueur
BIO-TP53-R175H- TP53 R175H point de prise de fonctionBIO-TP53-R273H- TP53 R273H point de contact avec l'ADNBIO-TP53-R282W- TP53 R282W point de perte partielle de fonctionnement