Document Detail

Amplification of chromosomal segment 4q12 in non-small cell lung cancer.
MedLine Citation:
PMID:  19755855     Owner:  NLM     Status:  MEDLINE    
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.
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 Wagner; Ignacio I Wistuba; Mark A Rubin; Matthew Meyerson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-07
Journal Detail:
Title:  Cancer biology & therapy     Volume:  8     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-12-28     Completed Date:  2010-06-25     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2042-50     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Non-Small-Cell Lung / genetics*,  pathology
Cell Line, Tumor
Chromosomes, Human, Pair 4*
Gene Amplification*
Gene Dosage
In Situ Hybridization, Fluorescence
Lung Neoplasms / genetics*,  pathology
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-kit / genetics*
Receptor, Platelet-Derived Growth Factor alpha / genetics*
Grant Support
5P20CA90578/CA/NCI NIH HHS; 5R01CA109038/CA/NCI NIH HHS; K08 CA134931/CA/NCI NIH HHS; P50 CA070907/CA/NCI NIH HHS; P50 CA070907-10/CA/NCI NIH HHS; P50 CA070907-11/CA/NCI NIH HHS; P50 CA070907-110009/CA/NCI NIH HHS; P50 CA070907-12/CA/NCI NIH HHS; P50 CA070907-120009/CA/NCI NIH HHS; T32 GM007753/GM/NIGMS NIH HHS
Reg. No./Substance:
EC Proteins c-kit; EC, Platelet-Derived Growth Factor alpha
Comment In:
Cancer Biol Ther. 2009 Nov;8(21):2051-3   [PMID:  19816149 ]

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