Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer. Academic Article uri icon

Overview

abstract

  • INTRODUCTION: 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). CONCLUSION: 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.

publication date

  • April 1, 2014

Research

keywords

  • Gene Amplification
  • Gene Dosage
  • Lung Neoplasms
  • Mutation
  • Receptor, Fibroblast Growth Factor, Type 1
  • Small Cell Lung Carcinoma

Identity

PubMed Central ID

  • PMC5705182

Scopus Document Identifier

  • 84919717017

Digital Object Identifier (DOI)

  • 10.1097/JTO.0000000000000089

PubMed ID

  • 24736083

Additional Document Info

volume

  • 9

issue

  • 4