TP53 R273H DNA-contact hotspot
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-TP53-R273H |
|---|---|
| Type | Biomarker |
| Aliases | DNA-contact mutantTP53 R273H DNA-contact hotspot mutationTP53 R273H — hotspot ДНК-контактуTP53 p.R273Hp53 R273H |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-NCCN-AML-2025 SRC-NCCN-BCELL-2025 SRC-NCCN-MM-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"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"} |
| Measurement | MethodTumor-tissue NGS panel (TP53 hotspot or full-gene); FFPE acceptable; ctDNA NGS for liquid biopsy Unitscategorical (positive | negative); VAF % for clonality assessment |
| Related biomarkers | BIO-TP53-MUTATION BIO-TP53-R175H BIO-TP53-R248Q BIO-TP53-R282W |
Notes
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.
Used By
Biomarker
BIO-TP53-R175H- TP53 R175H gain-of-function hotspotBIO-TP53-R248Q- TP53 R248Q DNA-contact hotspotBIO-TP53-R282W- TP53 R282W partial loss-of-function hotspot