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 1 Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan 2 Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan 3 Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan 4 Department of Surgery, Kinki University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan 5 Department of Hepato-Biliary-Pancreatic Surgery, Osaka City General Hospital, Miyakojima, Osaka, 534-0024, Japan 6 Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan 7 Department 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.