1. Amplification of chromosomal segment 4q12 in non-small cell lung cancer.
- Author
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Ramos AH, Dutt A, Mermel C, Perner S, Cho J, Lafargue CJ, Johnson LA, Stiedl AC, Tanaka KE, Bass AJ, Barretina J, Weir BA, Beroukhim R, Thomas RK, Minna JD, Chirieac LR, Lindeman NI, Giordano T, Beer DG, Wagner P, Wistuba II, Rubin MA, and Meyerson M
- Subjects
- Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Gene Dosage, Humans, In Situ Hybridization, Fluorescence, Lung Neoplasms pathology, Polymorphism, Single Nucleotide, Carcinoma, Non-Small-Cell Lung genetics, Chromosomes, Human, Pair 4, Gene Amplification, Lung Neoplasms genetics, Proto-Oncogene Proteins c-kit genetics, Receptor, Platelet-Derived Growth Factor alpha genetics
- 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.
- Published
- 2009
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