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

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

Author information

1
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
2
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
3
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
4
Center for Stem Cell Biology and Tissue Engineering, Department of Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
5
Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, 43210, Ohio, USA.
6
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
7
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
8
Departments of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21231, USA.
9
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21231, USA.
10
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. xiaowenh@pennmedicine.upenn.edu.
11
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. xiaowenh@pennmedicine.upenn.edu.
12
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. linzhang@pennmedicine.upenn.edu.
13
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA. linzhang@pennmedicine.upenn.edu.

Abstract

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.

PMID:
30760718
PMCID:
PMC6374416
DOI:
10.1038/s41467-019-08554-x
[Indexed for MEDLINE]
Free PMC Article

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