Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer
Author(s)
Dutt, Amit; Ramos, Alex H.; Hammerman, Peter S.; Mermel, Craig H.; Cho, Jeonghee; Sharifnia, Tanaz; Chande, Ajit; Tanaka, Kumiko Elisa; Stransky, Nicolas; Greulich, Heidi; Gray, Nathanael S.; Meyerson, Matthew L.; ... Show more Show less
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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.
Date issued
2011-06Department
Whitaker College of Health Sciences and Technology; Broad Institute of MIT and Harvard; Harvard University--MIT Division of Health Sciences and TechnologyJournal
PLoS ONE
Publisher
Public Library of Science
Citation
Dutt, Amit et al. “Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer.” Ed. Ming You. PLoS ONE 6 (2011): e20351.
Version: Final published version
ISSN
1932-6203