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

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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, paraffinembedded 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 FGFFGFR 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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Kaibori, M., Sakai, K., Ishizaki, M., Matsushima, H., de Velasco, M. A., Matsui, K., … Nishio, K. (2016). Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment. Oncotarget, 7(31), 49091–49098. https://doi.org/10.18632/oncotarget.10077

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