期刊
CANCER BIOLOGY & THERAPY
卷 8, 期 21, 页码 2042-2050出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.8.21.9764
关键词
NSCLC; lung cancer; PDGFRA; KIT; sunitinib; imatinib; amplification; 4q12
类别
资金
- Swiss National Science Foundation [PBZHB- 106297]
- National Cancer Institute [5R01CA109038, 5P20CA90578]
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 (NSCSCLC). 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 PDGFR alpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR alpha/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 alpha/KIT inhibitors.
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