FOXO3
Overview
FOXO3 is a FOXO-family transcription factor located at 6q21 that functions as a tumor suppressor downstream of the PI3K/AKT pathway. AKT-mediated phosphorylation excludes FOXO3 from the nucleus, suppressing its pro-apoptotic and cell cycle arrest programs. Deletion of the 6q21 locus, which contains FOXO3 and PRDM1, is enriched in SPOP-mutant prostate cancers, placing FOXO3 loss in a distinct molecular subtype characterized by ETS-negative disease.
Alterations observed in the corpus
- 6q21 deletions (containing FOXO3 and PRDM1) are enriched in SPOP-mutant prostate cancers (P = 3.4e-7) in a 112-tumor WES cohort (Broad); FOXO3 loss co-occurs with SPOP mutations as part of a coordinated genomic alteration pattern in ETS-negative prostate cancer PMID:22610119
- Mutation identified in ~7% of adenoid cystic carcinoma (ACC) cases; PI3K-pathway transcription factor PMID:23685749
- HD-defined TSG newly nominated as a breast-cancer Mut-driver via combined homozygous deletion and inactivating-mutation evidence; mutually exclusive with PIK3CA in breast tumors PMID:27161491
Cancer types (linked)
- PRAD (prostate adenocarcinoma): 6q21 deletion enriched in SPOP-mutant, ETS-negative prostate cancer; defines a molecular subtype with distinct co-alteration landscape PMID:22610119
Co-occurrence and mutual exclusivity
- Co-deleted with PRDM1 at 6q21; co-occurs with SPOP missense mutations; associated with absence of TMPRSS2-ERG rearrangements PMID:22610119
Therapeutic relevance
- No direct therapeutic implications reported in this corpus; PI3K/AKT pathway inhibitors may be relevant given FOXO3’s position downstream of AKT.
Open questions
- Whether 6q21 deletion drives tumor progression through FOXO3 loss, PRDM1 loss, or combined haploinsufficiency is not resolved PMID:22610119
Sources
This page was processed by crosslinker on 2026-05-09. - PMID:23685749
This page was processed by crosslinker on 2026-05-09. - PMID:27161491
This page was processed by wiki-cli on 2026-05-14.