癌症中大规模转录特征的遗传调控因子。
Genetic regulators of large-scale transcriptional signatures in cancer.
作者信息
Adler Adam S, Lin Meihong, Horlings Hugo, Nuyten Dimitry S A, van de Vijver Marc J, Chang Howard Y
机构信息
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
出版信息
Nat Genet. 2006 Apr;38(4):421-30. doi: 10.1038/ng1752. Epub 2006 Mar 5.
Abstract
Gene expression signatures encompassing dozens to hundreds of genes have been associated with many important parameters of cancer, but mechanisms of their control are largely unknown. Here we present a method based on genetic linkage that can prospectively identify functional regulators driving large-scale transcriptional signatures in cancer. Using this method we show that the wound response signature, a poor-prognosis expression pattern of 512 genes in breast cancer, is induced by coordinate amplifications of MYC and CSN5 (also known as JAB1 or COPS5). This information enabled experimental recapitulation, functional assessment and mechanistic elucidation of the wound signature in breast epithelial cells.
摘要
包含数十到数百个基因的基因表达特征已与癌症的许多重要参数相关联，但其调控机制在很大程度上尚不清楚。在此，我们提出一种基于遗传连锁的方法，该方法可前瞻性地识别驱动癌症中大规模转录特征的功能调节因子。使用这种方法，我们发现伤口反应特征，即乳腺癌中512个基因的不良预后表达模式，是由MYC和CSN5（也称为JAB1或COPS5）的协同扩增诱导的。这些信息使得能够在乳腺上皮细胞中对伤口特征进行实验重现、功能评估和机制阐明。
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