Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment
| Autor: | Yueying Wang, Yutian Pan, Meixiao Long, Ie Ming Shih, Xiaomin Zhong, Lin Zhang, Janos L. Tanyi, Junjie Jiang, Zhongyi Hu, Tian Li Wang, Xiaowen Hu, Xuepeng Wei, Kathleen T. Montone, Nicki Loo, Youyou Zhang, Junzhi Zhou, Yi Fan, Jiao Yuan, Tianli Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA Copy Number Variations Science General Physics and Astronomy Antineoplastic Agents 02 engineering and technology Computational biology Article General Biochemistry Genetics and Molecular Biology Histones 03 medical and health sciences Neoplasms Humans Tumor growth Molecular Targeted Therapy Epigenetics lcsh:Science Gene Histone Acetyltransferases Multidisciplinary biology Drug discovery Acetylation Genomics General Chemistry 021001 nanoscience & nanotechnology Anticancer drug 3. Good health Cancer treatment Gene Expression Regulation Neoplastic 030104 developmental biology Histone Mutation biology.protein lcsh:Q 0210 nano-technology Transcription Factors |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Targeting histone acetylation modulators (HAMPs) is a promising avenue of drug discovery in cancer research. Here, the authors integrate multi-dimensional genomic profiles to systematically investigate recurrent genomic alterations in HAMPs, identifying potential therapeutic targets for precision epigenetic treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|