MEF2B

Overview

MEF2B encodes Myocyte Enhancer Factor 2B, a MADS-box transcription factor that controls gene expression during development and differentiation. In germinal center B-cell (GCB) lymphomas, MEF2B is recurrently mutated at specific residues (K4, Y69, N81, D83) that impair its interaction with histone deacetylase complexes, thereby constitutively activating target gene transcription. MEF2B cooperates with CREBBP and EP300 in regulating histone acetylation at germinal center enhancers.

Alterations observed in the corpus

  • MEF2B was recurrently mutated in DLBCL and FL with hotspot missense mutations at K4, Y69, N81, and D83; alterations restricted to GCB subtype and cooperate with CREBBP/EP300 mutations in disrupting histone acetylation at germinal center enhancers PMID:21796119
  • MEF2B harbors recurrent somatic mutations in diffuse large B-cell lymphoma (DLBCL), identified by whole-exome sequencing of 55 tumors PMID:22343534
  • Recurrent exon-2 p.K23R missense mutation in 6/187 (3.2%) MCL; restricted to SOX11-positive tumors; hotspot in conserved MADS-box domain PMID:24145436

Cancer types (linked)

  • DLBCL (GCB subtype): MEF2B hotspot mutations at K4, Y69, N81, D83 disrupt interaction with CABIN1 co-repressor, leading to constitutive transcriptional activation PMID:21796119
  • FL: MEF2B mutations also recurrent, suggesting a shared role in the GCB differentiation block common to both entities PMID:21796119

Co-occurrence and mutual exclusivity

  • MEF2B mutations co-occur with CREBBP and EP300 mutations in GCB DLBCL/FL, implying convergent disruption of germinal center transcriptional programs PMID:21796119

Therapeutic relevance

  • MEF2B-driven transcriptional dysregulation may be targetable through histone deacetylase inhibitors; no direct clinical data yet.

Open questions

  • The precise mechanism by which MEF2B hotspot mutations drive lymphomagenesis and whether they are sufficient as single events remains to be established.

Sources

  • PMID:21796119 — Whole-genome/exome sequencing of non-Hodgkin lymphomas (DLBCL/FL)

This page was processed by crosslinker on 2026-05-09. - PMID:22343534

This page was processed by crosslinker on 2026-05-09. - PMID:24145436

This page was processed by crosslinker on 2026-05-09.