title: Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer.
abstract: BACKGROUND
  There remains a significant therapeutic need for small-cell lung cancer (SCLC). We and others have reported high frequency of copy number gains in cytogenetic bands encoding fibroblast growth factor receptor 1 (FGFR1) in SCLC tumors and cell lines.
  
  
  METHODS
  Thirteen SCLC cell lines and 68 SCLC patient tumor samples were studied for FGFR1 amplification. Growth inhibition assays were performed using PD173074, a pan-FGFR inhibitor to determine the correlation between FGFR1 expression and drug sensitivity.
  
  
  RESULTS
  We did not detect FGFR1 mutations in SCLC cell lines. Focal amplification of FGFR1 gene was found in five tumor samples (7%), with high-level focal amplification in only one tumor sample (1%). Amplification owing to polysomy of chromosome 8, where FGFR1 locates, was observed in 22 tumor samples (32%). There was no correlation between FGFR1 gene copy number and messenger RNA expression or protein expression in SCLC cells. FGFR inhibitor sensitivity correlated with FGFR1 copy number determined by real-time polymerase chain reaction assay (r= -0.79; p = 0.01).
  
  
  CONCLUSIONS
  FGFR1 gene mutations and focal amplification are rare in SCLC, but polysomy of chromosome 8 is relatively common. FGFR1 copy number gain predicts sensitivity to FGFR inhibition, and FGFR expression correlates inversely with chemosensitivity.
authors.affiliation: *Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; †Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and ‡Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Anish
authors.initials: A
authors.lastname: Thomas
authors.forename: Jih-Hsiang
authors.initials: JH
authors.lastname: Lee
authors.forename: Zied
authors.initials: Z
authors.lastname: Abdullaev
authors.forename: Kang-Seo
authors.initials: KS
authors.lastname: Park
authors.forename: Marbin
authors.initials: M
authors.lastname: Pineda
authors.forename: Lola
authors.initials: L
authors.lastname: Saidkhodjaeva
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.forename: Yisong
authors.initials: Y
authors.lastname: Wang
authors.forename: Svetlana D
authors.initials: SD
authors.lastname: Pack
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011743:Pyrimidines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: C115711:PD 173074; D011743:Pyrimidines; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
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