FOXN4

Overview

FOXN4 (Forkhead Box N4) encodes a developmental transcription factor. In malignant peripheral nerve sheath tumors (MPNSTs) with PRC2 loss, FOXN4 is aberrantly re-expressed as a consequence of H3K27me3 loss at its promoter, representing a developmentally suppressed homeobox master regulator unleashed by PRC2 inactivation.

Alterations observed in the corpus

• Aberrantly upregulated in PRC2-loss MPNSTs; promoter H3K27me3 is restored (and transcript levels reduced) after SUZ12 reintroduction in SUZ12-deficient ST88-14 cells; identified as a direct PRC2 target in MPNST PMID:25240281.

Cancer types (linked)

• MPNST: PRC2-repressed developmental master regulator aberrantly re-expressed in EED/SUZ12-deficient tumors PMID:25240281.

Co-occurrence and mutual exclusivity

• Overexpression co-occurs with EED or SUZ12 inactivation and H3K27me3 loss in MPNST PMID:25240281.

Therapeutic relevance

• Not directly targeted therapeutically; its re-expression marks PRC2-loss tumors and could help characterize the downstream oncogenic transcriptional program PMID:25240281.

Open questions

• Whether FOXN4 re-expression contributes functionally to MPNST growth or serves primarily as a biomarker of PRC2 loss is unknown PMID:25240281.

Sources

• PMID:25240281

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