APC

Overview

APC (Adenomatous Polyposis Coli) is a canonical tumor suppressor and negative regulator of the WNT/beta-catenin signaling pathway. Germline APC mutations cause familial adenomatous polyposis and predispose to colorectal cancer. In the corpus, APC alterations are noted in hepatocellular carcinoma (HCC) cfDNA profiling as a component of WNT pathway disruption.

Alterations observed in the corpus

  • APC alterations detected in 8% of advanced HCC patients by cfDNA profiling (MSK-ACCESS panel, 51 patients); classified as a WNT pathway alteration PMID:37769223.
  • 13 mutations in 11 LUAD tumours; first report of recurrent APC mutations in lung adenocarcinoma (previously known only in colorectal, squamous-cell, and small-cell lung cancer); part of Wnt pathway alteration. PMID:18948947
  • Subclonal APCQ879* detected in CRC C106-resistant cells; various APC alterations detected in patient ctDNA at resistance to KRASG12C + EGFR inhibition PMID:36355783
  • APC truncated at aa 1309 in the A1309 CRC cell model; APC mutations implicated as potential biomarker of 5-FU resistance PMID:36334560
  • APC mutations detected in pancreatic cystic neoplasms by whole-exome sequencing, implicating Wnt pathway dysregulation PMID:22158988
  • APC somatic mutations identified in breast cancer WES of 100 tumors as part of the driver gene landscape PMID:22722201
  • APC mutations observed in medulloblastoma WGS of 37 tumors (PCGP), implicating Wnt signaling disruption PMID:22722829
  • APC alterations observed in prostate cancer WES of 112 tumors (Michigan cohort) PMID:22722839
  • APC is the most frequently mutated gene in colorectal adenocarcinoma, altered in the majority of 276 TCGA CRC tumors profiled by WES, consistent with its role as a gatekeeper tumor suppressor in the Wnt pathway PMID:22810696
  • Mutated in colorectal cancer WES study (Genentech, 74 tumors); identified alongside RSPO2/3 fusions in comprehensive genomic profiling PMID:22895193
  • Mutated in TCGA lung squamous cell carcinoma cohort (178 tumors) PMID:22960745
  • Beta-catenin-pathway mutation in EAC; APC + CDH1 or APC + AXIN1 co-mutations observed in two individual tumors; Wnt/beta-catenin alterations present in only 9% of EACs (esca_broad), contrasting with CRC PMID:23525077
  • Somatic mutation in 2/23 (9%) pancreatic carcinomas with acinar differentiation; consistent with prior reports of APC/beta-catenin pathway involvement in acinar cell carcinoma PMID:24293293
  • Somatic mutation reported in the HCC molecular landscape (WES, n=1,289); part of the non-actionable trunk-driver set PMID:24798001
  • GAPPS syndrome driven by APC promoter 1B variants is included in the differential diagnosis of familial/hereditary gastric cancer; standard multigene GC panel includes APC PMID:24816255
  • Beta-catenin pathway alteration in non-hypermutated gastric tumours; APC and CTNNB1 mutations co-occur in the Wnt pathway dysregulation landscape of gastric adenocarcinoma PMID:25079317
  • Higher prevalence than TCGA in metastatic CRC; private mutations in 7 patients (mostly secondary to a shared clonal hit); in one patient, primary-private nonsense was rendered phenotypically equivalent in the metastasis by chromosomal deletion of the APC locus PMID:25164765
  • Candidate dark-matter driver in papillary thyroid carcinoma; among chromatin-remodeling and additional driver alterations across 97/402 (24.1%) PTC tumors in the TCGA PTC cohort PMID:25417114
  • Recurrently mutated driver in gastric cancer (GC); participates in Wnt signaling pathway; observed alongside PIK3CA, SMAD4, MYC, and KRAS mutations in a 294-patient Tianjin WES cohort PMID:25583476
  • Classic CRC driver gene studied as comparison baseline in African American vs. Caucasian CRC cohort (103 AA, 129 Caucasian); mutation rates reported across both ethnic groups PMID:25583493
  • Recurrently mutated WNT-pathway component in PDA; co-mutated with AXIN1 and AXIN2, nominating tankyrase inhibitors (XAV939) as therapeutic candidates PMID:25855536
  • Recurrently altered in mCRPC for the first time; part of WNT pathway alterations also including CTNNB1, RNF43, ZNRF3, and RSPO2 fusions PMID:26000489
  • Truncating mutations observed in primary prostate cancer as part of beta-catenin pathway alterations; co-occurs with CTNNB1 mutations PMID:26544944
  • Mutated in periampullary adenocarcinomas (duodenal/DUOAC subtype) and contributed to elevated WNT-pathway mutation frequency; APC and SOX9 were the primary WNT-pathway drivers in this site PMID:26804919
  • Single truncating APC p.Q1529X mutation found in 117 advanced thyroid tumors (PDTC/ATC); the study explicitly failed to replicate prior reports of frequent WNT-pathway alterations in ATC PMID:26878173
  • Wnt-pathway alteration observed in cisplatin-resistant germ cell tumors alongside AXIN1 and FAT1 PMID:27646943
  • APC R1114* germline variant in hepatoblastoma diagnostic of familial adenomatous polyposis (FAP); APC E1554fs in poorly differentiated carcinoma diagnostic of newly recognized Gardner syndrome; APC V1822D returned as a variant of uncertain significance in Ewing sarcoma PMID:28007021
  • APC mutation rate lower in esophageal adenocarcinoma (EAC) vs CIN gastric — pan-esophageal/gastroesophageal cancer genomic landscape study PMID:28052061
  • Cited as a lineage-restricted driver in colorectal cancer, contrasted with pan-cancer drivers TP53/PIK3CA, in the MSK-IMPACT prospective profiling cohort (n=10,945) PMID:28481359
  • V2194Ffs*5 frameshift mutation detected in 1/19 sequenced 1p/19q-codeleted anaplastic oligodendrogliomas; incidental alteration alongside canonical IDH1/TERT/CIC/FUBP1 drivers PMID:28472509
  • Pathogenic germline APC variants found in 3 CTNNB1-wild-type WNT medulloblastomas — Turcot syndrome predisposition; APC germline testing warranted when WNT MB is suspected without CTNNB1 mutation PMID:28726821
  • APC is a non-DNA-repair presumed pathogenic germline mutation (PPGM) gene in 6 of 500 metastatic cancer patients (9.5%), significantly enriched vs. ExAC controls in the MET500 pan-cancer cohort PMID:28783718
  • APC enriched in both metastatic prostate cancer states relative to locoregional disease, implicating it as a driver of metastasis; co-occurs with CTNNB1 and RNF43 as Wnt-pathway alterations PMID:28825054
  • Mutated in 79% of MSS mCRC tumors; a recurrent intronic chr5:112151184 A>G splice-acceptor mutation expands the oncogenic spectrum into intronic regions; oncogenic APC alterations were a positive prognostic factor in mCRC (HR=0.57) PMID:29316426.
  • APC is confirmed as an established driver in prostate cancer with metastasis-vs-primary enrichment quantified across 1,013 prostate cancers (prad_p1000). PMID:29610475

Cancer types (linked)

  • HCC — APC mutations detected by liquid biopsy in 8% of advanced HCC; part of WNT pathway disruption landscape alongside CTNNB1 PMID:37769223.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No direct therapeutic targeting of APC in HCC is reported in the corpus. WNT pathway alterations (including APC) were detected in actionable-alteration assessments but are not FDA-approved targets in HCC PMID:37769223.

Open questions

  • Whether APC versus CTNNB1 mutation defines distinct WNT pathway activation states with different therapeutic vulnerabilities in HCC is not addressed in the corpus PMID:37769223.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:18948947

This page was processed by crosslinker on 2026-05-14. - PMID:36355783

This page was processed by crosslinker on 2026-05-14. - PMID:36334560

This page was processed by crosslinker on 2026-05-14. - PMID:22158988

This page was processed by crosslinker on 2026-05-14. - PMID:22722201

This page was processed by crosslinker on 2026-05-14. - PMID:22722829

This page was processed by crosslinker on 2026-05-14. - PMID:22722839

This page was processed by crosslinker on 2026-05-14. - PMID:22810696

This page was processed by crosslinker on 2026-05-14. - PMID:22895193

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:23525077

This page was processed by crosslinker on 2026-05-14. - PMID:24293293

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:24816255

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25164765

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:25583476

This page was processed by crosslinker on 2026-05-14. - PMID:25583493

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26000489

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26804919

This page was processed by entity-page-writer on 2026-05-15. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15. - PMID:28052061

This page was processed by entity-page-writer on 2026-05-15. - PMID:28481359

This page was processed by entity-page-writer on 2026-05-15. - PMID:28472509

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:28783718

This page was processed by wiki-cli on 2026-05-15. - PMID:28825054

This page was processed by wiki-cli on 2026-05-15. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.