FOXA1

Overview

FOXA1 is a forkhead/pioneer transcription factor with lineage-defining roles in endoderm-derived epithelia and recurrent involvement in lung, breast, and prostate cancer.

Alterations observed in the corpus

  • Altered more often in LUAD metastases than in matched primary tumors PMID:37084736.
  • Enriched in LUAD primary tumors from patients who later developed brain metastases compared to BM−/EM− primaries PMID:37591896.
  • Involved in ETV1-FOXA1 gene fusions in prostate cancer PDX models (MD Anderson MDA PCa PDX series) PMID:38488813.
  • Identified as a recurrent post-treatment alteration and Gleason/metastasis-association gene in PRAD within the MSK-CHORD real-world cohort (n = 3,211 prostate cancer patients); co-listed with AR, CDK12, and NKX3-1 as markers of treatment-driven genomic evolution PMID:39506116.
  • Binding sites at distal enhancers hypomethylated in breast cancer metastases; implicated in estrogen-mediated suppression of cell-adhesion genes PMID:36585450
  • Missense mutations restricted to the Forkhead domain near the DNA-binding surface in 4/111 prostate cancer exomes; FOXA1 modulates AR-driven transcription and activates CDKN1B expression PMID:22610119
  • FOXA1 identified as a recurrently mutated transcription factor in prostate cancer WES cohort (Michigan, 112 tumors); mutations cluster in the forkhead domain and may cooperate with ETS fusions PMID:22722839
  • Recurrently mutated in luminal breast cancer (TCGA, 510 tumors); mutations cluster in the forkhead DNA-binding domain PMID:23000897
  • Recurrent clonal/early point mutations in prostate cancer, confirmed early in the progression path (cross-confirmed against PMID:22610119) PMID:23622249
  • Low oestrogen receptor/FOXA1 signalling characteristic of the PARADIGM cluster 3 (copy-number-high) endometrial cancer subtype PMID:23636398
  • FOXA1 identified as a significantly mutated gene (SMG) at ≤8% frequency in muscle-invasive bladder cancers in TCGA urothelial carcinoma comprehensive genomic characterization PMID:24476821
  • Expressed mutation observed in CRPC cell line MSK-PCa2; consistent with recurrence of FOXA1 mutations in castration-resistant prostate cancer PMID:25201530
  • AR pathway regulator in mCRPC; FOXA1 mutations cluster near the end of the Forkhead DNA-binding domain PMID:26000489
  • Recurrent fork-head W2-region mutations (I176, D226 spatial hotspot) in ILC (7%); mutations associated with increased FOXA1 mRNA expression, suggesting activating rather than loss-of-function mechanism; mutually exclusive with GATA3 mutations PMID:26451490
  • Mutated in 3-4% of primary prostate cancers; missense mutations cluster in the winged-helix DNA-binding domain but not at DNA-contact residues; mutually exclusive with most other subtype-defining alterations; FOXA1-mutant tumors have elevated AR transcriptional output PMID:26544944
  • AR co-activator alterations (including FOXA1, NCOR1, NCOR2, ZBTB16) enriched in CRPC-Adeno (21 cases) vs. CRPC-NE; FOXA1 alterations support retained AR signaling axis in adenocarcinoma subtype PMID:26855148
  • Enriched in earlier disease states alongside SPOP in prostate cancer (defining a possibly androgen-deprivation-sensitive subset); also noted as a context gene in disease-state enrichment analyses; locoregional frequency higher than TCGA due to selection bias toward aggressive disease in the MSK-IMPACT cohort (n=451 patients) PMID:28825054
  • Strongly expressed in luminal subtypes of MIBC; identified as a luminal driver by regulon analysis; co-driver alongside GATA3 and PPARG in the luminal transcriptional program PMID:28988769
  • Confirmed established prostate cancer driver; significantly enriched in metastatic vs primary PRAD tumors in the 1,013-sample WES meta-cohort (prad_p1000); tumors lacking ETS fusion, IDH1, SPOP, CUL3, and FOXA1 alterations are enriched for epigenetic-regulator mutations (p=0.007). PMID:29610475

Cancer types (linked)

  • LUAD — metastasis-enriched and associated with brain-metastatic trajectory PMID:37084736 PMID:37591896.
  • PRAD — gene fusion partner (ETV1-FOXA1) in PDX models PMID:38488813; recurrent post-treatment alteration enriched after prior systemic therapy and associated with Gleason score in MSK-CHORD PMID:39506116.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Not reported in the corpus.

Open questions

  • None flagged in the corpus.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

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

This page was processed by crosslinker on 2026-05-14. - PMID:26855148

This page was processed by wiki-cli on 2026-05-14. - PMID:28825054

This page was processed by wiki-cli on 2026-05-15. - PMID:28988769

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

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