Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer

PLoS One. 2011;6(6):e20351. doi: 10.1371/journal.pone.0020351. Epub 2011 Jun 7.


Background: Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.

Methodology/principal findings: Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes-WHSC1L1, LETM2, and FGFR1-is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.

Conclusions/significance: These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Amplification* / drug effects
  • Gene Knockdown Techniques
  • Genetic Loci / genetics
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Open Reading Frames / genetics
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Small Interfering / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism


  • 3' Untranslated Regions
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1