Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Apr;2(2):92-100.
doi: 10.3978/j.issn.2218-6751.2013.03.03.

FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications

Hans-Ulrich Schildhaus  1 , Lucia Nogova  2 , Jürgen Wolf  2 , Reinhard Buettner  1
Affiliations
Review

FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications

Hans-Ulrich Schildhaus et al. Transl Lung Cancer Res. 2013 Apr.

Abstract

Fibroblast growth factor receptor 1 (FGFR1) is a type 4 receptor tyrosine kinase. The receptor and its ligands play an important role in development and physiology. However, constitutive activation of FGFR1 by gene amplification, translocation or mutation is associated with various malignancies as, for example, breast cancer or myeloproliferative diseases. We have recently reported that FGFR1 amplification occurs in 20% of pulmonary squamous cell carcinomas, and preclinical tests have shown that these alterations are therapeutically tractable. These findings make FGFR1 amplification a potential biomarker for lung cancer treatment. Squamous cell carcinomas of the lung are characterized by an uneven FGFR1 gene copy number distribution. Therefore, fluorescence in situ hybridization assays need to address focality and heterogeneity of FGFR1 in these tumors. Here, we review our proposal for a reading and evaluation strategy. Furthermore, we highlight the emerging landscape of clinical trials with selective and unselective FGFR inhibitors and provide first response data from early clinical trials.

Keywords: FISH; Lung cancer; fibroblast growth factor receptor 1 (FGFR1); squamous cell carcinoma.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Fluorescence in situ hybridization for detection of FGFR1 amplification in pulmonary squamous cell carcinomas. A. In this tumor, FGFR1 (green) and chromosome 8 (CEN8, orange) copies are more or less evenly distributed. Only occasionally, microclusters are seen (arrow); B. Heterogeneity occurs frequently in these tumors. Beside tumor cells with normal or only slight increase in copy numbers, there are many tumor cell nuclei with tight clusters of amplified FGFR1, some of which are indicated by arrows. Note that the occurrence of FGFR1 clusters is not necessarily related to the size of the nuclei.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403. - PubMed
    1. Perez-Moreno P, Brambilla E, Thomas R, et al. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res 2012;18:2443-51. - PubMed
    1. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8. - PubMed
    1. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010;2:62ra93. - PMC - PubMed
    1. Schildhaus HU, Heukamp LC, Merkelbach-Bruse S, et al. Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol 2012;25:1473-80. - PMC - PubMed