Nature Genetics 38, 421 - 430 (2006)
Published online: 5 March 2006; | doi:10.1038/ng1752
Genetic regulators of large-scale transcriptional signatures in cancerAdam S Adler1, 2, 5, Meihong Lin1, 5, Hugo Horlings3, Dimitry S A Nuyten3, 4, Marc J van de Vijver3
& Howard Y Chang1, 21
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA. 2
Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA. 3
Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 4
Radiation Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 5
These authors contributed equally to this work.
Correspondence should be addressed to Howard Y Chang howchang@stanford.edu 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.
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