A genomic strategy to elucidate modules of oncogenic pathway signaling networks.

Journal Article (Journal Article)

Recent studies have emphasized the importance of pathway-specific interpretations for understanding the functional relevance of gene alterations in human cancers. Although signaling activities are often conceptualized as linear events, in reality, they reflect the activity of complex functional networks assembled from modules that each respond to input signals. To acquire a deeper understanding of this network structure, we developed an approach to deconstruct pathways into modules represented by gene expression signatures. Our studies confirm that they represent units of underlying biological activity linked to known biochemical pathway structures. Importantly, we show that these signaling modules provide tools to dissect the complexity of oncogenic states that define disease outcomes as well as response to pathway-specific therapeutics. We propose that this model of pathway structure constitutes a framework to study the processes by which information propogates through cellular networks and to elucidate the relationships of fundamental modules to cellular and clinical phenotypes.

Full Text

Duke Authors

Cited Authors

  • Chang, JT; Carvalho, C; Mori, S; Bild, AH; Gatza, ML; Wang, Q; Lucas, JE; Potti, A; Febbo, PG; West, M; Nevins, JR

Published Date

  • April 2009

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 104 - 114

PubMed ID

  • 19362539

Pubmed Central ID

  • PMC2694616

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2009.02.030


  • eng