Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
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.
在抗癌药物发现工作中，越来越重视针对组蛋白乙酰化调节剂的靶向治疗。在这里，我们全面分析了癌症基因组图谱队列中编码组蛋白乙酰化调节剂蛋白（HAMPs）的基因的基因组改变，观察到 HAMPs 具有高频的焦点拷贝数改变和反复突变，而 HAMPs 的转录融合是常见成人癌症中相对罕见的基因组事件。总的来说，至少有 1 种癌症类型中 86.3%（63/73）的 HAMPs 存在反复改变，并且在多种癌症类型中发现了 16 个 HAMPs，包括 9 个研究较少的 HAMPs，被鉴定为潜在的治疗靶点。例如，BRD9 的反复焦点扩增发生在 9 种癌症中，BRD9 的遗传缺失抑制肿瘤生长。我们对大规模癌症标本队列中 HAMPs 的系统基因组分析可能有助于识别和优先考虑潜在的药物靶点，并为精准治疗选择合适的患者。
