POLD1 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-POLD1-HYPERMUTATOR |
|---|---|
| Type | Biomarker |
| Aliases | POLD1 EDM (exonuclease domain mutation)POLD1 гіпермутаторний фенотип (мутація proofreading-домену)POLD1-mutated hypermutator |
| 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": "6-12 (proofreading / exonuclease domain)", "functional_impact": "loss of proofreading fidelity → ultra-high TMB, hypermutator phenotype (analogous to POLE-EDM)", "gene": "POLD1", "variant_type": "missense (pathogenic exonuclease-domain)"} |
| Measurement | MethodNGS panel covering POLD1 exonuclease domain. Pathogenic somatic or germline variants confer hypermutator phenotype. Less common than POLE-EDM but mechanistically analogous; co-call with TMB. Unitscategorical (pathogenic_EDM | non-pathogenic / wild-type) |
| Related biomarkers | BIO-POLE-HYPERMUTATOR BIO-DMMR-IHC BIO-MSI-STATUS |
Notes
Less frequent than POLE-EDM but mechanistically equivalent. Grouped with POLE in TCGA/TransPORTEC integrated endometrial classification. Triggers the same Stage I de-escalation logic (RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK + IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION). Germline variants implicate PPAP — refer to genetic counseling.
Used By
Biomarker
BIO-POLE-HYPERMUTATOR- POLE 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 (...