Amplification of chromosomal segment 4q12 in non-small cell lung cancer

Alex H. Ramos, Amit Dutt, Craig Mermel, Sven Perner, Jeonghee Cho, Christopher J. Lafargue, Laura A. Johnson, Ann Cathrin Stiedl, Kumiko E. Tanaka, Adam J. Bass, Jordi Barretina, Barbara A. Weir, Rameen Beroukhim, Roman K. Thomas, John D. Minna, Lucian R. Chirieac, Neal I. Lindeman, Thomas Giordano, David G. Beer, Patrick WagnerIgnacio I. Wistuba, Mark A. Rubin, Matthew Meyerson

Research output: Contribution to journalArticle

75 Scopus citations

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 (NSCscLCc). Ssingle 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 PDGFR? activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR?/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 PDGFR?/KIT inhibitors.

Original languageEnglish (US)
Pages (from-to)2042-2050
Number of pages9
JournalCancer Biology and Therapy
Volume8
Issue number21
DOIs
StatePublished - Nov 1 2009

Keywords

  • 4q12
  • Amplification
  • Imatinib
  • KIT
  • Lung cancer
  • NSCLC
  • PDGFRA
  • Sunitinib

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Ramos, A. H., Dutt, A., Mermel, C., Perner, S., Cho, J., Lafargue, C. J., Johnson, L. A., Stiedl, A. C., Tanaka, K. E., Bass, A. J., Barretina, J., Weir, B. A., Beroukhim, R., Thomas, R. K., Minna, J. D., Chirieac, L. R., Lindeman, N. I., Giordano, T., Beer, D. G., ... Meyerson, M. (2009). Amplification of chromosomal segment 4q12 in non-small cell lung cancer. Cancer Biology and Therapy, 8(21), 2042-2050. https://doi.org/10.4161/cbt.8.21.9764