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Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening
Open accessAbstract
Summary We screened 124 genes that are amplified in human 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.
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The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Chromosome aberrations in solid tumors
Albertson, D. G., Collins, C., McCormick, F., & Gray, J. W. (2003) · Nature Genetics · doi:10.1038/ng1215 · Cited by 812
A Mouse Model of Hepatocellular Carcinoma
Nicholes, K., Guillet, S., Tomlinson, E., Hillan, K., Wright, B., Frantz, G. D., Pham, T. A., Dillard-Telm, L., Tsai, S. P., Stephan, J.-P., et al. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)61177-7 · Cited by 359
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Llovet, J. M., Zucman-Rossi, J., Pikarsky, E., Sangro, B., Schwartz, M., Sherman, M., & Gores, G. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.18 · Cited by 2,531
Schulze, K., Imbeaud, S., Letouzé, E., Alexandrov, L. B., Calderaro, J., Rebouissou, S., Couchy, G., Meiller, C., Shinde, J., Soysouvanh, F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3252 · Cited by 1,803
Guichard, C., Amaddeo, G., Imbeaud, S., Ladeiro, Y., Pelletier, L., Maad, I. B., Calderaro, J., Bioulac-Sage, P., Letexier, M., Degos, F., et al. (2012) · Nature Genetics · doi:10.1038/ng.2256 · Cited by 1,453
Genetic landscape and biomarkers of hepatocellular carcinoma
Zucman-Rossi, J., Villanueva, A., Nault, J.-C., & Llovet, J. M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.061 · Cited by 1,325
Mechanisms of HBV-induced hepatocellular carcinoma
Levrero, M., & Zucman-Rossi, J. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.021 · Cited by 1,052
Metadata
- Authors
- Sawey, E. T., Chanrion, M., Cai, C., Wu, G., Zhang, J., Zender, L., Zhao, A., Busuttil, R. W., Yee, H., Stein, L., French, D. M., Finn, R. S., Lowe, S. W., & Powers, S.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 19
- Issue
- 3
- Pages
- 347-358
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2095943598
- Cited by
- 436
- References
- 4
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sawey, E. T., Chanrion, M., Cai, C., Wu, G., Zhang, J., Zender, L., Zhao, A., Busuttil, R. W., Yee, H., Stein, L., French, D. M., Finn, R. S., Lowe, S. W., & Powers, S. (2011). Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening. Cancer Cell. https://doi.org/10.1016/j.ccr.2011.01.040
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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