EN1

Overview

EN1 (Engrailed Homeobox 1) is a developmental transcription factor with roles in neuronal and musculoskeletal development. In cancer, EN1 has been reported as a biomarker of high-grade adenoid cystic carcinoma (ACC). In the chromatin landscape study of ACC by Drier et al. (2016), EN1 was identified as a putative MYB-driven transcriptional regulator, placing it downstream of the MYB enhancer-hijacking oncogenic mechanism that drives most ACCs.

Alterations observed in the corpus

  • EN1 identified as a putative MYB-driven transcription regulator and established high-grade ACC biomarker in a chromatin profiling and whole-genome sequencing study of 20 adenoid cystic carcinomas (acyc_mgh_2016); EN1 was among the top transcriptional regulators in the MYB peak-associated gene set. PMID:26829750

Cancer types (linked)

  • ACYC (adenoid cystic carcinoma): EN1 is a high-grade ACC biomarker; identified as a putative target of the MYB oncogenic transcriptional program based on MYB ChIP-seq binding data from 3 ACC primagrafts. Cohort: 20 ACCs (5 primary specimens + 8 primagrafts + additional biopsies) (acyc_mgh_2016). PMID:26829750

Co-occurrence and mutual exclusivity

  • EN1 is downstream of the MYB enhancer-hijacking mechanism present in 15/20 (75%) ACCs. In the same study, MYB cooperates with TP63 in low-grade (grade 2) ACC myoepithelial cells and with Notch in high-grade (grade 3) ACC luminal epithelial cells; EN1 as a high-grade biomarker may reflect the Notch-driven grade-3 transcriptional program. PMID:26829750

Therapeutic relevance

  • EN1 is a biomarker of high-grade ACC rather than a direct therapeutic target in this study. High-grade (grade 3) ACC characterized by Notch pathway activation is insensitive to BET bromodomain inhibition (JQ1) in primagraft models; Notch inhibition is proposed for this subtype. Whether EN1 functional activity contributes to grade-3 ACC biology beyond its use as a biomarker was not tested. PMID:26829750

Open questions

  • Whether EN1 is a driver of high-grade ACC biology (downstream of MYB/Notch) or a passenger marker of the high-grade transcriptional state is unresolved. The MYB-binding evidence (ChIP-seq at the EN1 locus) supports a regulatory relationship, but functional studies in ACC are lacking. PMID:26829750

Sources

  • PMID:26829750 — Drier et al. (2016), chromatin profiling and WGS of 20 ACCs, MYB enhancer-hijacking mechanism and transcriptional program (acyc_mgh_2016).

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