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Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer.


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.

SUBMITTER: Thomas A 

PROVIDER: S-EPMC5705182 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer.

Thomas Anish A   Lee Jih-Hsiang JH   Abdullaev Zied Z   Park Kang-Seo KS   Pineda Marbin M   Saidkhodjaeva Lola L   Miettinen Markku M   Wang Yisong Y   Pack Svetlana D SD   Giaccone Giuseppe G  

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20140401 4


<h4>Introduction</h4>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.<h4>Methods</h4>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 FGFR  ...[more]

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