CHD8
Overview
CHD8 (Chromodomain Helicase DNA Binding Protein 8) is an ATP-dependent chromatin remodeling enzyme belonging to the CHD family. CHD8 regulates transcription by remodeling nucleosome positioning and is a critical regulator of Wnt/beta-catenin signaling, p53 target gene activation, and cell cycle progression. In cancer, CHD8 functions are context-dependent; somatic mutations have been reported in multiple malignancies including B-cell lymphomas.
Alterations observed in the corpus
- CHD8 was identified as a driver-gene cluster member in DLBCL within the signaling, cell growth, B-cell development, and transcription/translation functional groups, based on whole-exome sequencing of 1001 de novo DLBCL patients (150 recurrent driver genes). PMID:28985567
Cancer types (linked)
- DLBCLNOS: CHD8 mutations were identified as a recurrent driver event in DLBCL among 150 driver genes from integrative WES and RNA-seq of 1001 patients. Pairwise co-occurrence or mutual exclusivity relationships with other drivers were not specifically reported for CHD8. PMID:28985567
Co-occurrence and mutual exclusivity
- No specific co-occurrence or mutual exclusivity patterns for CHD8 were reported in the DLBCL cohort. It clusters with other signaling and transcriptional regulators among the 150 driver genes. PMID:28985567
Therapeutic relevance
- CHD8 was not among the 9 CRISPR-validated essential driver genes identified as direct targets of approved or trial-stage drugs in the DLBCL study; its therapeutic tractability in DLBCL remains to be established. PMID:28985567
Open questions
- Whether CHD8 mutations are enriched in ABC vs GCB DLBCL, and whether CHD8 loss confers CRISPR essentiality in established DLBCL cell lines, was not reported in this study. PMID:28985567
Sources
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