Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment

Nat Commun. 2019 Feb 13;10(1):733. doi: 10.1038/s41467-019-08554-x.


A growing emphasis in anticancer drug discovery efforts has been on targeting histone acetylation modulators. Here we comprehensively analyze the genomic alterations of the genes encoding histone acetylation modulator proteins (HAMPs) in the Cancer Genome Atlas cohort and observe that HAMPs have a high frequency of focal copy number alterations and recurrent mutations, whereas transcript fusions of HAMPs are relatively rare genomic events in common adult cancers. Collectively, 86.3% (63/73) of HAMPs have recurrent alterations in at least 1 cancer type and 16 HAMPs, including 9 understudied HAMPs, are identified as putative therapeutic targets across multiple cancer types. For example, the recurrent focal amplification of BRD9 is observed in 9 cancer types and genetic depletion of BRD9 inhibits tumor growth. Our systematic genomic analysis of HAMPs across a large-scale cancer specimen cohort may facilitate the identification and prioritization of potential drug targets and selection of suitable patients for precision treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Antineoplastic Agents / therapeutic use
  • DNA Copy Number Variations / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genomics / methods*
  • Histone Acetyltransferases / antagonists & inhibitors
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism*
  • Humans
  • Molecular Targeted Therapy / methods
  • Mutation*
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Antineoplastic Agents
  • BRD9 protein, human
  • Histones
  • Transcription Factors
  • Histone Acetyltransferases