Project description:In cancer, proto-oncogenes are often altered by genomic amplification. Recent studies have highlighted a role for PDGFRA as an oncogene in non-small cell lung cancer. To characterize 4q12 copy number status in NSCLC, both previously published (Weir et al. PMID 17982442) and unpublished Affymetrix 250K SNP array data for 733 NSCLC samples (628 primary samples, 105 cell lines) were evaluated for copy number aberrations. 4q12 amplifications overlapping the PDGFRA/KIT locus were observed in 31 (4.2%) NSCLC samples. SNP array and FISH analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFRα activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRα/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 PDGFRα/KIT inhibitors.
Project description:To identify chromosomal alterations in ATL, SNP array analyses were performed in 19 leukemia cell samples from ATL patients and 9 ATL-related cell lines. ATL displayed complex chromosomal abnormalities, but it contained recurrent chromosomal amplification and deletion, including 14q11 and 14q32, which may be associated with the development of ATL. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved peripheral blood samples and from cell line samples.