An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors. Academic Article uri icon

Overview

abstract

  • To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.

publication date

  • June 15, 2009

Research

keywords

  • Adenocarcinoma
  • Dual-Specificity Phosphatases
  • ErbB Receptors
  • Gene Expression Profiling
  • Lung Neoplasms
  • Mitogen-Activated Protein Kinase Phosphatases
  • Mutation

Identity

PubMed Central ID

  • PMC2722688

Scopus Document Identifier

  • 68349139723

Digital Object Identifier (DOI)

  • 10.1038/onc.2009.135

PubMed ID

  • 19525976

Additional Document Info

volume

  • 28

issue

  • 31