Genetic regulators of large-scale transcriptional signatures in cancer.
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.
Adler
Adam S
AS
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Lin
Meihong
M
Horlings
Hugo
H
Nuyten
Dimitry S A
DS
van de Vijver
Marc J
MJ
Chang
Howard Y
HY
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D005455:Fluorescent Antibody Technique; D016259:Genes, myc; D008040:Genetic Linkage; D006801:Humans; D018895:Microsatellite Repeats; D014158:Transcription, Genetic / Q000235:genetics*