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

被引：35

作者：

Kaibori, Masaki ^{[1
]}

Sakai, Kazuko ^{[2
]}

Ishizaki, Morihiko ^{[1
]}

Matsushima, Hideyuki ^{[1
]}

De Velasco, Marco A. ^{[2
]}

Matsui, Kosuke ^{[1
]}

Iida, Hiroya ^{[1
]}

Kitade, Hiroaki ^{[1
]}

Kwon, A-Hon ^{[1
]}

Nagano, Hiroaki ^{[3
]}

Wada, Hiroshi ^{[3
]}

Haji, Seiji ^{[4
]}

Tsukamoto, Tadashi ^{[5
]}

Kanazawa, Akishige ^{[5
]}

Takeda, Yutaka ^{[6
]}

Takemura, Shigekazu ^{[7
]}

Kubo, Shoji ^{[7
]}

Nishio, Kazuto ^{[2
]}

机构：

[1] Kansai Med Univ, Hirakata Hosp, Dept Surg, Hirakata, Osaka 5731010, Japan

[2] Kinki Univ, Fac Med, Dept Genome Biol, Osakasayama, Osaka 5898511, Japan

[3] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Osaka 5650871, Japan

[4] Kinki Univ, Fac Med, Dept Surg, Osakasayama, Osaka 5898511, Japan

[5] Osaka City Gen Hosp, Dept Hepatobiliary Pancreat Surg, Miyakojima, Osaka 5340024, Japan

[6] Kansai Rosai Hosp, Dept Surg, Amagasaki, Hyogo 6608511, Japan

[7] Osaka City Univ, Grad Sch Med, Dept Hepatobiliary Pancreat Surg, Osaka 5588585, Japan

来源：

ONCOTARGET | 2016年 / 7卷 / 31期

基金：

日本学术振兴会;

关键词：

FGF19; sorafenib; copy number gain; hepatocellular carcinoma; MULTIPLE LUNG METASTASES; TUMOR PROGRESSION; SOLID TUMORS; LIVER-CANCER; ANGIOGENESIS; INHIBITORS; PATHWAY; GENES;

D O I：

10.18632/oncotarget.10077

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：49091 / 49098

页数：8

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