CHD1

Overview

CHD1 (Chromodomain Helicase DNA Binding Protein 1) encodes an ATP-dependent chromatin remodeler that binds H3K4me3-marked promoters and facilitates transcription elongation. Located at 5q21, CHD1 deletion is a recurrent event in prostate cancer and is enriched in SPOP-mutant tumors, suggesting a cooperative role in a distinct molecular subtype of ETS-negative prostate cancer.

Alterations observed in the corpus

  • Located at the 5q21 locus enriched for deletions in SPOP-mutant prostate tumors; encodes a chromatin-modifying enzyme; identified in a WES study of 112 prostate tumors (Broad Institute cohort) PMID:22610119
  • CHD1 deletions and mutations identified in prostate cancer WES of 112 tumors (Michigan cohort); CHD1 loss associated with ETS-negative tumors PMID:22722839
  • Focal deletion or disruptive rearrangement defines an ETS-negative prostate carcinoma subset with chromothripsis-like intra-chromosomal chains in late-replicating, GC-poor DNA; CHD1 loss correlates with elevated recurrent SCNAs (p=1.5×10⁻⁸) in an extended 199-tumor cohort PMID:23622249
  • Focal homozygous deletion with complete protein loss in MSK-PCa2, MSK-PCa4, and MSK-PCa7 prostate cancer cell lines derived from CRPC PMID:25201530
  • Recurrent deletion (8q copy-number loss) in metastatic castration-resistant prostate cancer (mCRPC) PMID:26000489
  • Co-deleted with SPOP-mutant subtype at 5q15-q21 in primary prostate cancer; MAP3K7 and CHD1 co-deletion at 6q12-22 associated with aggressive ETS-negative disease PMID:26544944
  • CHD1 listed as a recurrent mCRPC driver mutation consistent with prior reports, identified in multi-metastasis WGS/array CGH autopsy study (63 men, multiple metastatic sites per patient) PMID:26928463

Cancer types (linked)

  • PRAD (prostate adenocarcinoma): Deletion at 5q21 is recurrent in SPOP-mutant tumors; co-occurring with 6q21 deletions, defining a distinct ETS-negative molecular subtype PMID:22610119

Co-occurrence and mutual exclusivity

  • Co-deleted with SPOP mutations in prostate cancer; 5q21 deletions are enriched in SPOP-mutant tumors (P-value significant), and these tumors lack TP53 lesions, PIK3CA, and ETS rearrangements PMID:22610119

Therapeutic relevance

  • CHD1 loss has been associated with sensitivity to PARP inhibitors and AR-directed therapies in preclinical models; functional chromatin remodeling deficiency may influence response to DNA damage repair-targeting agents.

Open questions

  • Whether CHD1 deletion is a driver or a passenger event co-selected with SPOP mutations at 5q21 requires further investigation.
  • The functional interaction between CHD1 loss and SPOP mutation in prostate carcinogenesis remains to be mechanistically defined.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26928463

This page was processed by entity-page-writer on 2026-05-15.