Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening

被引：450

作者：

Sawey, Eric T. ^{[1
]}

Chanrion, Maia ^{[1
]}

Cai, Chunlin ^{[1
]}

Wu, Guanming ^{[2
]}

Zhang, Jianping ^{[1
]}

Zender, Lars ^{[1
]}

Zhao, Alice ^{[3
]}

Busutti, Ronald W. ^{[4
]}

Yee, Herman ^{[5
]}

Stein, Lincoln ^{[1
,2
]}

French, Dorothy M. ^{[6
]}

Finn, Richard S. ^{[3
]}

Lowe, Scott W. ^{[1
]}

Powers, Scott ^{[1
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[2] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada

[3] Univ Calif Los Angeles, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA

[5] NYU, Sch Med, Dept Pathol, Bellevue Hosp Ctr, New York, NY 10016 USA

[6] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA

来源：

CANCER CELL | 2011年 / 19卷 / 03期

关键词：

SERINE/THREONINE KINASE PIM-2; CYCLIN D1; HEPATOCELLULAR-CARCINOMA; TUMOR-GROWTH; GENES; TRANSFORMATION; AMPLIFICATION; EXPRESSION; RECEPTOR; FIBROBLAST-GROWTH-FACTOR-19;

D O I：

10.1016/j.ccr.2011.01.040

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

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 I:hat CCND1 is the main driving oncogene of this common amplicon (15% frequency in HOC), both forward-transformation assays and RNAi-mediated inhibition in human HOC 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 amplification could be an effective biomarker for patients most likely to respond to anti-FGF19 therapy.

引用

页码：347 / 358

页数：12

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