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TP53 R248Q DNA-Kontakt Hotspot

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IDBIO-TP53-R248Q
ArtBiomarker
Aliase
DNA-KontaktmutantTP53 R248Q DNA-Kontakt Hotspot-MutationTP53 R248Q — hotspot ДНК-контактуTP53 p.R248Qp53 R248Q
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": "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"}
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-R175H BIO-TP53-R273H BIO-TP53-R282W

Anmerkungen

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.

Verwendet von

Biomarker