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J Thorac Oncol. 2014 Apr;9(4):567-71. doi: 10.1097/JTO.0000000000000089.

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

Author information

1
*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.

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.

PMID:
24736083
PMCID:
PMC5705182
DOI:
10.1097/JTO.0000000000000089
[Indexed for MEDLINE]
Free PMC Article

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