POLE hypermutator phenotype (proofreading-domain mutation)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-POLE-HYPERMUTATOR |
|---|---|
| Type | Biomarker |
| Aliases | POLE EDM (exonuclease domain mutation)POLE гіпермутаторний фенотип (мутація proofreading-домену)POLE-mutated hypermutatorPOLE-ultramutated |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESGO-ENDOMETRIAL-2025 SRC-ESMO-ENDOMETRIAL-2022 SRC-NCCN-UTERINE-2025 |
Biomarker Facts
| Biomarker type | clinical_composite |
|---|---|
| Mutation details | {"exon": "9-14 (proofreading / exonuclease domain)", "functional_impact": "loss of proofreading fidelity → ultra-high TMB (>100 mut/Mb), hypermutator phenotype", "gene": "POLE", "variant_type": "missense (pathogenic exonuclease-domain)"} |
| Measurement | MethodNGS panel covering POLE exonuclease domain (codons 268-471). Pathogenic variants per TransPORTEC / TCGA list (e.g., P286R, V411L, S297F, A456P, S459F, others) confer hypermutator phenotype. Some panels co-call TMB which serves as supportive evidence. Unitscategorical (pathogenic_EDM | non-pathogenic / wild-type) |
| Related biomarkers | BIO-POLD1-HYPERMUTATOR BIO-DMMR-IHC BIO-MSI-STATUS |
Notes
Endometrial-specific TCGA molecular subtype (~7% of endometrial cancers). Pathogenic exonuclease-domain (EDM) variants drive hypermutator phenotype with TMB typically >100 mut/Mb. PORTEC-3 / TransPORTEC stratification showed Stage I POLE-EDM tumors do not benefit from adjuvant therapy — observation only. POLE-mutated endometrial carcinoma also enriches for immune infiltration and may respond to ICI in advanced setting (covered by existing dMMR/MSI-H / TMB-high indications). This biomarker primarily enables Stage I de-escalation via RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK + IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION.
Used By
Biomarker
BIO-POLD1-HYPERMUTATOR- POLD1 hypermutator phenotype (proofreading-domain mutation)
Indications
IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION- IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION
Red flag
RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK- Stage I endometrial carcinoma with pathogenic POLE or POLD1 exonuclease-domain mutation (...