title: Amplification of chromosomal segment 4q12 in non-small cell lung cancer.
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.
authors.affiliation: Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Ramos
authors.forename: Amit
authors.initials: A
authors.lastname: Dutt
authors.forename: Craig
authors.initials: C
authors.lastname: Mermel
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Jeonghee
authors.initials: J
authors.lastname: Cho
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lafargue
authors.forename: Laura A
authors.initials: LA
authors.lastname: Johnson
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Stiedl
authors.forename: Kumiko E
authors.initials: KE
authors.lastname: Tanaka
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
authors.forename: Jordi
authors.initials: J
authors.lastname: Barretina
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Weir
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Lucian R
authors.initials: LR
authors.lastname: Chirieac
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.forename: Thomas
authors.initials: T
authors.lastname: Giordano
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.forename: Patrick
authors.initials: P
authors.lastname: Wagner
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002894:Chromosomes, Human, Pair 4; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha