APC loss-of-function mutation / truncation

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-APC`
Type	Biomarker
Aliases	APC mutationМутація втрати функції APC (усікання)
Status	reviewed 2026-05-04 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-CRC-2024` `SRC-NCCN-COLON-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"exon": "multiple; hotspot cluster region codons 1286–1513 (mutation cluster region, MCR)", "functional_impact": "loss-of-function", "gene": "APC", "variant_type": "loss-of-function (nonsense, frameshift, large deletion, splice; MCR hotspot for somatic CRC)"}
Measurement	MethodTumor NGS panel; germline NGS (blood) for FAP/AFAP; IHC (nuclear β-catenin accumulation as surrogate)
Actionability lookup	{"gene": "APC", "variant": "loss_of_function"}
Related biomarkers	`BIO-CTNNB1` `BIO-KRAS` `BIO-TP53` `BIO-SMAD4`

Notes

APC (Adenomatous Polyposis Coli) is the gatekeeper tumor suppressor of the WNT/β-catenin pathway. APC forms the destruction complex with AXIN1/2, GSK-3β, and CK1α that phosphorylates β-catenin (CTNNB1) at exon 3 residues (S33/S37/T41/S45) targeting it for proteasomal degradation. Loss of APC → β-catenin accumulates, translocates to the nucleus, activates TCF/LEF transcription of MYC, CCND1, and pro-proliferative genes. Frequency: somatic APC mutation in ~80% of sporadic CRC (earliest event in adenoma-carcinoma sequence). Germline: FAP (familial adenomatous polyposis) — >100 adenomas, nearly 100% CRC risk by 40y without colectomy; AFAP (attenuated FAP) — fewer adenomas, later onset. Clinical relevance: APC mutation is diagnostic/prognostic context in CRC; no APC-targeted therapy approved. Surrogate: nuclear β-catenin by IHC confirms WNT pathway activation when sequencing unavailable.

Used By

Actionability

BMA-APC-CRC - APC somatic loss-of-function mutations occur in ~80% of sporadic colorectal carcinomas (C...