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首页> 外文期刊>Cancer Cell >Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening.
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Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening.

机译:通过肿瘤基因组筛选确定靶向扩增的FGF19的肝癌治疗策略。

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摘要

We screened 124 genes that are amplified in human hepatocellular carcinoma (HCC) using a mouse hepatoblast model and identified 18 tumor-promoting genes, including CCND1 and its neighbor on 11q13.3, FGF19. Although it is widely assumed that CCND1 is the main driving oncogene of this common amplicon (15% frequency in HCC), both forward-transformation assays and RNAi-mediated inhibition in human HCC cells established that FGF19 is an equally important driver gene in HCC. Furthermore, clonal growth and tumorigenicity of HCC cells harboring the 11q13.3 amplicon were selectively inhibited by RNAi-mediated knockdown of CCND1 or FGF19, as well as by an anti-FGF19 antibody. These results show that 11q13.3 amplification could be an effective biomarker for patients most likely to respond to anti-FGF19 therapy.
机译:我们使用小鼠成肝细胞模型筛选了在人类肝细胞癌(HCC)中扩增的124个基因,并鉴定了18个促进肿瘤的基因,包括CCND1及其在11q13.3上的邻居,FGF19。尽管人们普遍认为CCND1是这种常见扩增子的主要驱动癌基因(在HCC中为15%的频率),但是在人HCC细胞中进行正向转化分析和RNAi介导的抑制作用都可以确定FGF19在HCC中同样重要。此外,RNAi介导的CCND1或FGF19的敲除以及抗FGF19抗体选择性抑制具有11q13.3扩增子的HCC细胞的克隆生长和致瘤性。这些结果表明,11q13.3扩增可能是最可能对抗FGF19治疗产生反应的患者的有效生物标志物。

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