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FGFR1 expression, not gene amplification, predicts FGFR inhibitor sensitivity in head and neck squamous cell cancer cells

Göke, Friederike and Franzen, Alina and Sharma, Rakesh and Bode, Maike and von Maessenhausen, Anne and Heasley, Lynn E and Perner, Sven (2015) FGFR1 expression, not gene amplification, predicts FGFR inhibitor sensitivity in head and neck squamous cell cancer cells. Clinical cancer research, 21 (19). pp. 4356-4364. ISSN 26015511

Abstract

FGFR1 has emerged as a novel target in human cancers. Based on frequent FGFR1 gene amplification in lung cancers and head and neck squamous cell cancers (HNSCC), FGFR1 gene copy number (GCN) is being deployed as the biomarker in clinical trials of FGFR-specific TKIs. Using a panel of HNSCC cell lines, we demonstrate that sensitivity to the FGFR-specific TKI, NVP-BGJ398, is associated with FGFR1 mRNA and protein expression levels, but not FGFR1 amplification status. We deployed assays for FGFR1 mRNA and GCN to analyze primary HNSCC tumors and observed frequent (31%) elevation of FGFR1 mRNA, although only 20% of these also exhibited elevated FGFR1 GCN. While 18% of HNSCC tumors exhibited increased FGFR1 GCN, only 35% of these expressed FGFR1 mRNA. Our results demonstrate that FGFR1 expression, not gene amplification, per se, may be a more accurate biomarker of HNSCC sensitivity to FGFR-specific TKIs.

Item Type: Article
Date Deposited: 13 Apr 2017 00:45
Last Modified: 13 Apr 2017 00:45
URI: https://oak.novartis.com/id/eprint/10077

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