CHD2

Overview

CHD2 (Chromodomain Helicase DNA Binding Protein 2) encodes an ATP-dependent chromatin remodeling enzyme belonging to the CHD family. CHD2 regulates nucleosome positioning and gene expression, and is implicated in DNA damage response and developmental transcription programs. Recurrent CHD2 driver mutations have been identified in high-risk meningioma (MG3/MG4 molecular groups) in an integrative molecular classification of this tumor type.

Alterations observed in the corpus

  • Novel recurrent driver mutations enriched in MG3/MG4 (high-risk) meningioma molecular groups in a comprehensive integrative molecular classification of 565 meningiomas; CHD2 alterations implicate chromatin remodeling dysregulation as a mechanism of aggressive meningioma behavior PMID:34433969.
  • Truncating mutation in chromatin-remodeling gene cluster in ACC; part of cluster collectively mutated in 12/24 cases PMID:23778141
  • Single frameshift mutation identified in sinonasal AdCC (1/21 sequenced cases); part of the long tail of singleton mutations in this cohort; chromatin-remodeling gene PMID:24418857
  • CHD2 enriched in IGHV-mutated CLL subtype — one of only three drivers (along with del(13q) and MYD88) enriched in IGHV-mutated rather than IGHV-unmutated CLL in a 538-sample WES study PMID:26466571

Cancer types (linked)

  • MNG: CHD2 recurrent driver mutations enriched in MG3 and MG4 meningioma groups, which are associated with higher risk of recurrence and worse outcomes compared to MG1 and MG2; CHD2 mutations co-occur with KDM6A and PTEN alterations in this context PMID:34433969.

Co-occurrence and mutual exclusivity

  • CHD2 mutations co-occur with KDM6A mutations and PTEN alterations in MG3/MG4 meningiomas; NF2 mutations are uncommon in this group, distinguishing it from the benign MG1 subtype PMID:34433969.

Therapeutic relevance

  • No direct therapeutic targeting of CHD2 in meningioma is reported in the corpus; MG4 meningiomas harboring CHD2/KDM6A/PTEN alterations are the target population for vorinostat (HDAC inhibitor) investigation, which showed selective in vitro and in vivo efficacy PMID:34433969.

Open questions

  • Whether CHD2 loss-of-function is a driver vs. co-passenger of aggressive meningioma biology, and whether chromatin remodeling-targeted therapies could exploit this vulnerability, has not been tested.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:26466571

This page was processed by crosslinker on 2026-05-14.