CTNNB1 activating mutation (β-catenin)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-CTNNB1 |
|---|---|
| Type | Biomarker |
| Aliases | CTNNB1 / beta-catenin mutationАктивуюча мутація CTNNB1 (β-катенін) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESGO-ENDOMETRIAL-2025 SRC-NCCN-HCC-2025 SRC-NCCN-UTERINE-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "3 (phosphorylation/destruction box: codons 32–45)", "functional_impact": "activating", "gene": "CTNNB1", "variant_type": "missense activating (S33C, S37F, T41A, S45P, D32Y most common; prevent GSK-3β-mediated phosphorylation and proteasomal degradation)"} |
| Measurement | MethodTumor NGS panel (exon 3 sequencing); IHC (nuclear β-catenin accumulation — surrogate for mutation, ~95% concordance with exon 3 hotspot) |
| Actionability lookup | {"gene": "CTNNB1", "variant": "activating_mutation"} |
| Related biomarkers | None declared |
Notes
CTNNB1 encodes β-catenin, a dual-function protein: (1) structural (adherens junctions, E-cadherin complex); (2) transcriptional (WNT signaling effector, activating TCF/LEF target genes including MYC, CCND1). Activating mutations in exon 3 prevent destruction complex (APC/AXIN/GSK-3β/CK1) from phosphorylating β-catenin, leading to nuclear accumulation and constitutive WNT target gene activation. Key clinical contexts: (1) Endometrial cancer (EC): CTNNB1 exon 3 mutations in ~25–30%, predominantly in endometrioid histology. The TCGA molecular classification: CTNNB1 mutation is enriched in the NSMP (No Specific Molecular Profile) and POLE-ultramutated groups. Critical prognostic finding: CTNNB1 mutations, particularly in FIGO stage I-II EC, associate with L1CAM overexpression and high risk of recurrence despite low stage — this subgroup may benefit from adjuvant chemotherapy (EC-specific risk stratification per ESGO/ESMO/ESTRO 2023). CTNNB1-mutant NSMP EC is classified as intermediate/ high-intermediate risk. (2) HCC: CTNNB1 mutations in ~20–30%, associated with the β-catenin activated molecular subtype (cholestatic, hepatocytic differentiation). CTNNB1-mutant HCC has lower response r...
Used By
Actionability
BMA-CTNNB1-ENDOMETRIAL- CTNNB1 exon 3 mutations occur in ~25–30% of endometrial carcinoma (EC), predominantly end...
Biomarker
BIO-APC- APC loss-of-function mutation / truncation