TP53 R273H ponto de contacto com ADN
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| ID | BIO-TP53-R273H |
|---|---|
| Tipo | Biomarcador |
| Alegais | Mutante de contacto com ADNTP53 R273H mutação de hotspot de contacto com DNATP53 R273H — hotspot ДНК-контактуTP53 p.R273Hp53 R273H |
| 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": "8", "functional_impact": "loss_of_function (DNA-contact residue lost) + gain-of-function (chemoresistance, migration, GOF transcriptional rewiring)", "gene": "TP53", "gene_hugo_id": "11998", "hgvs_coding": "c.818G>A", "hgvs_protein": "p.R273H", "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-R175H BIO-TP53-R248Q BIO-TP53-R282W |
Notas
R273 is among the top three most-mutated TP53 codons (with R175 and R248). DNA-contact class: R273 directly contacts the DNA major groove via its guanidinium side chain. R→H substitution preserves the thermal stability of the protein fold (distinguishing it from structural R175H) but eliminates specific DNA binding. R273H is one of the best-characterized GOF p53 mutants — promotes chemoresistance via NF-κB activation, drives invasion/metastasis through CXCR4 and RhoA pathways, reprograms metabolism (mevalonate pathway upregulation). Clinical implications mirror the TP53-mutant class: AML/MDS — venetoclax-azacitidine + alloSCT consideration; CLL/MCL — contraindicates chemoimmuno; MM — high-risk cytogenetics composite routes to quadruplet. Notably, R273H tumors are particularly resistant to platinum chemotherapy across solid-tumor types per multiple correlative analyses — relevant for ovarian, lung, esophageal cancer treatment selection.
Usado por
Biomarcador
BIO-TP53-R175H- TP53 R175H ganho de funçãoBIO-TP53-R248Q- TP53 R248Q Hotspot de contato com DNABIO-TP53-R282W- TP53 R282W ponto de perda parcial de função