Amplification of chromosomal segment 4q12 in non-small cell lung cancer. Academic Article uri icon

Overview

abstract

  • In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFRalpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRalpha/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFRalpha/KIT inhibitors.

publication date

  • November 7, 2009

Research

keywords

  • Carcinoma, Non-Small-Cell Lung
  • Chromosomes, Human, Pair 4
  • Gene Amplification
  • Lung Neoplasms
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha

Identity

PubMed Central ID

  • PMC2833355

Scopus Document Identifier

  • 73549108711

Digital Object Identifier (DOI)

  • 10.4161/cbt.8.21.9764

PubMed ID

  • 19755855

Additional Document Info

volume

  • 8

issue

  • 21