Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment
Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment
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DOI：
10.1038/s41467-019-08554-x
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发表时间：
2019-02-13
影响因子：
16.6
通讯作者：
Zhang, Lin
中科院分区：
文献类型：
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作者：
Hu, Zhongyi;Zhou, Junzhi;Zhang, Lin
在抗癌药物发现工作中，靶向组蛋白乙酰化调节剂的工作越来越受到重视。在这里，我们综合分析了癌症基因组图谱中编码组蛋白乙酰化调节蛋白(HAMPS)基因的基因组变化，观察到HAMPS具有高频率的焦点拷贝数变化和反复突变，而HAMPS的转录本融合在常见的成人癌症中相对罕见。总体而言，86.3%(63/73)的HAMP至少在一种癌症类型中有反复改变，16种HAMP，包括9种未被研究的HAMP，被确定为多种癌症类型的假定治疗靶点。例如，在9种癌症类型中观察到BRD9的反复局部扩增，并且BRD9的基因缺失抑制了肿瘤的生长。我们对大规模癌症样本队列中HAMP的系统基因组分析可能有助于识别和优先选择潜在的药物靶点，并选择合适的患者进行精确治疗。
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.