ASH2L

Overview

ASH2L encodes a component of the MLL (KMT2) histone H3K4 methyltransferase complex, acting as a core subunit required for catalytic activity and target gene regulation. In prostate cancer, ASH2L is mutated and functionally required for androgen receptor (AR)-mediated transcription; siRNA knockdown of ASH2L inhibits AR signaling, placing it in a network of chromatin modulators that co-regulate AR programs in castration-resistant prostate cancer.

Alterations observed in the corpus

  • ASH2L mutations identified in prostate cancer WES of 112 tumors (Michigan cohort) as part of a chromatin/histone-modifying gene cluster including KDM6A, ASXL1, and KMT2A PMID:22722839
  • siRNA knockdown of ASH2L inhibited AR signaling >7.5-fold (p<0.001), demonstrating a functional requirement of the MLL complex for AR-mediated transcription in prostate cancer PMID:22722839

Cancer types (linked)

  • Prostate cancer (PRAD): ASH2L mutated and functionally essential for AR transcriptional program; part of a broader chromatin modifier landscape in castration-resistant prostate cancer PMID:22722839

Co-occurrence and mutual exclusivity

  • ASH2L mutations co-occur with other MLL complex member mutations (KMT2A, KMT2D) and AR alterations in the Michigan prostate cancer cohort PMID:22722839

Therapeutic relevance

  • ASH2L-dependent AR signaling suggests that targeting the MLL histone methyltransferase complex may suppress AR transcriptional programs in castration-resistant prostate cancer PMID:22722839

Open questions

  • Whether ASH2L mutations directly impair MLL complex activity or alter AR co-activation in prostate tumors is not established from WES data alone; functional studies in patient-derived models are needed PMID:22722839

Sources

This page was processed by entity-page-writer on 2026-05-06.