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. 2016 Aug 2;7(31):49091-49098.
doi: 10.18632/oncotarget.10077.

Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment

Masaki Kaibori  1 , Kazuko Sakai  2 , Morihiko Ishizaki  1 , Hideyuki Matsushima  1 , Marco A De Velasco  2 , Kosuke Matsui  1 , Hiroya Iida  1 , Hiroaki Kitade  1 , A-Hon Kwon  1 , Hiroaki Nagano  3 , Hiroshi Wada  3 , Seiji Haji  4 , Tadashi Tsukamoto  5 , Akishige Kanazawa  5 , Yutaka Takeda  6 , Shigekazu Takemura  7 , Shoji Kubo  7 , Kazuto Nishio  2
Affiliations

Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment

Masaki Kaibori et al. Oncotarget. .

Abstract

The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.

Keywords: FGF19; copy number gain; hepatocellular carcinoma; sorafenib.

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Conflict of interest statement

None of the authors have any potential conflicts of interest to report.

Figures

Figure 1
Figure 1. Frequency of FGF19 gene amplification in solid cancers
Gene mutation and copy number alterations in the FGF19 gene were sought using the cBioPortal for Cancer Genomics (http://www.cbioportal.org/public-portal/). The arrow indicates the amplification of FGF19 in HCC.
See this image and copyright information in PMC

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