Thomas Anish, Lee Jih-Hsiang, Abdullaev Zied, Park Kang-Seo, Pineda Marbin, Saidkhodjaeva Lola, Miettinen Markku, Wang Yisong, Pack Svetlana D, Giaccone Giuseppe
*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.
J Thorac Oncol. 2014 Apr;9(4):567-71. doi: 10.1097/JTO.0000000000000089.
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.
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.
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).
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.
小细胞肺癌（SCLC）仍存在巨大的治疗需求。我们和其他研究人员报告称，在SCLC肿瘤和细胞系中，编码成纤维细胞生长因子受体1（FGFR1）的细胞遗传带中拷贝数增加的频率很高。
对13个SCLC细胞系和68个SCLC患者肿瘤样本进行FGFR1扩增研究。使用泛FGFR抑制剂PD173074进行生长抑制试验，以确定FGFR1表达与药物敏感性之间的相关性。
我们在SCLC细胞系中未检测到FGFR1突变。在5个肿瘤样本（7%）中发现FGFR1基因的局灶性扩增，仅在1个肿瘤样本（1%）中发现高水平局灶性扩增。在22个肿瘤样本（32%）中观察到由于FGFR1所在的8号染色体多体性导致的扩增。SCLC细胞中FGFR1基因拷贝数与信使RNA表达或蛋白质表达之间无相关性。FGFR抑制剂敏感性与通过实时聚合酶链反应测定法确定的FGFR1拷贝数相关（r = -0.79；p = 0.01）。
FGFR1基因突变和局灶性扩增在SCLC中罕见，但8号染色体多体性相对常见。FGFR1拷贝数增加预示着对FGFR抑制的敏感性，且FGFR表达与化学敏感性呈负相关。
