Characterization of Fibroblast Growth Factor Receptor 1 in Small-Cell Lung Cancer

被引：28

作者：

Thomas, Anish ^{[1
]}

Lee, Jih-Hsiang ^{[1
]}

Abdullaev, Zied ^{[2
]}

Park, Kang-Seo ^{[1
]}

Pineda, Marbin ^{[3
]}

Saidkhodjaeva, Lola ^{[2
]}

Miettinen, Markku ^{[2
]}

Wang, Yisong ^{[1
]}

Pack, Svetlana D. ^{[2
]}

Giaccone, Giuseppe ^{[1
]}

机构：

[1] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA

[2] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA

[3] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2014年 / 9卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Small-cell lung cancer; FGFR1; Focal amplification; Copy number gain; GENOME;

D O I：

10.1097/JTO.0000000000000089

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：567 / 571

页数：5

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