POLE Hypermutator Phänotyp (Proofreading-Domain-Mutation)
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-POLE-HYPERMUTATOR |
|---|---|
| Art | Biomarker |
| Aliase | POLE EDM (Exonuclease-Domänenmutation)POLE гіпермутаторний фенотип (мутація proofreading-домену)POLE-mutierter HypermutatorPOLE-ultramutiert |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Erkrankungen | DIS-ENDOMETRIAL |
| Quellen | SRC-ESGO-ENDOMETRIAL-2025 SRC-ESMO-ENDOMETRIAL-2022 SRC-NCCN-UTERINE-2025 |
Biomarker-Fakten
| Biomarker-Typ | clinical_composite |
|---|---|
| Angaben zur Mutation | {"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)"} |
| Messung | VerfahrenNGS-Panel, das POLE exonuclease-Domäne (Codons 268-471) abdeckt. Pathogene Varianten nach TransPORTEC / TCGA-Liste (z.B. P286R, V411L, S297F, A456P, S459F, andere) verleihen Hypermutator-Phänotyp. Einige Panels co-Call TMB, die als unterstützende Beweise dient. Einheitencategorical (pathogenic_EDM | non-pathogenic / wild-type) |
| Verwandte Biomarker | BIO-POLD1-HYPERMUTATOR BIO-DMMR-IHC BIO-MSI-STATUS |
Anmerkungen
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.
Verwendet von
Biomarker
BIO-POLD1-HYPERMUTATOR- POLD1-Hypermutator-Phänotyp (Proofreading-Domain-Mutation)BIO-POLE-GERMLINE- POLE keimlinienpathogene Variante (Korrekturlesebereich)
Anwendungsgebiet
IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION- IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION
Warnhinweis
RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK- Stadium I Endometriumkarzinom mit pathogener POLE- oder POLD1-Exonuklease-Domain-Mutation (...