NOTCH2 mutation (PEST domain truncating)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-NOTCH2-MUTATION |
|---|---|
| Type | Biomarker |
| Aliases | NOTCH2 mutationМутація NOTCH2 (PEST-домен, скорочуючі) |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-CIVIC SRC-NCCN-BCELL-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"functional_impact": "stabilization of activated NOTCH2 intracellular domain → constitutive NF-κB + marginal-zone differentiation signaling", "gene": "NOTCH2", "variant_type": "frameshift / nonsense in PEST domain (exon 34)"} |
| Measurement | MethodNGS panel covering NOTCH2 PEST domain (exon 34) Unitscategorical (positive | negative) |
| Related biomarkers | None declared |
Notes
Cross-disease relevance: - **Splenic marginal-zone lymphoma (SMZL)** (~25%): defining recurrent driver alongside KLF2; associated with shorter time-to- treatment + worse OS. Currently informational; no NOTCH2-targeted therapy in MZL standard-of-care. - **DLBCL (BN2 / C1 cluster)** (~20% of cases): NOTCH2 PEST mutation + BCL6 fusion + cluster of marginal-zone-derived events define the LymphGen BN2 subtype. BN2 has favorable outcome with R-CHOP and appears intermediate-sensitive to BTKi. - **Nodal MZL / MALT** (~5-10%): less frequent; subset marker. - **CLL** (~5%): rare; not a treatment driver. LymphGen BN2-classifier component for DLBCL; engine uses presence to support BN2 subtype call (combined with BCL6 fusion + other marginal-zone-derived events). Standalone treatment-changing impact modest at MVP. `multi_allele_mvp` skip reason: PEST exon-34 truncating events have multiple recurring sites without a single canonical hotspot — same pattern as NOTCH1 PEST.
Used By
No reverse references found in the YAML corpus.