Oncotarget

Research Papers:

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

Masaki Kaibori, Kazuko Sakai, Morihiko Ishizaki, Hideyuki Matsushima, Marco A. De Velasco, Kosuke Matsui, Hiroya Iida, Hiroaki Kitade, A-Hon Kwon, Hiroaki Nagano, Hiroshi Wada, Seiji Haji, Tadashi Tsukamoto, Akishige Kanazawa, Yutaka Takeda, Shigekazu Takemura, Shoji Kubo and Kazuto Nishio _

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Oncotarget. 2016; 7:49091-49098. https://doi.org/10.18632/oncotarget.10077

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Abstract

Masaki Kaibori1,*, Kazuko Sakai2,*, Morihiko Ishizaki1, Hideyuki Matsushima1, Marco A. De Velasco2, Kosuke Matsui1, Hiroya Iida1, Hiroaki Kitade1, A-Hon Kwon1, Hiroaki Nagano3, Hiroshi Wada3, Seiji Haji4, Tadashi Tsukamoto5, Akishige Kanazawa5, Yutaka Takeda6, Shigekazu Takemura7, Shoji Kubo7, Kazuto Nishio2

1Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan

2Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan

3Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan

4Department of Surgery, Kinki University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan

5Department of Hepato-Biliary-Pancreatic Surgery, Osaka City General Hospital, Miyakojima, Osaka, 534-0024, Japan

6Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan

7Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, 558-8585, Japan

*These authors have contributed equally to this work

Correspondence to:

Kazuto Nishio, email: knishio@med.kindai.ac.jp

Keywords: FGF19, sorafenib, copy number gain, hepatocellular carcinoma

Received: November 04, 2015    Accepted: May 17, 2016    Published: June 15, 2016

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.


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