Characterizing genomic alterations in cancer by complementary functional associations

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Characterizing genomic alterations in cancer by complementary functional associations

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Title: Characterizing genomic alterations in cancer by complementary functional associations
Author: Kim, J. W.; Botvinnik, O. B.; Abudayyeh, O.; Birger, C.; Rosenbluh, J.; Shrestha, Y.; Abazeed, M. E.; Hammerman, P. S.; DiCara, D.; Konieczkowski, D. J.; Johannessen, C. M.; Liberzon, A.; Alizad-Rahvar, A. R.; Alexe, G.; Aguirre, A.; Ghandi, M.; Greulich, H.; Vazquez, F.; Weir, B. A.; Van Allen, E. M.; Tsherniak, A.; Shao, D. D.; Zack, T. I.; Noble, M.; Getz, G.; Beroukhim, R.; Garraway, L. A.; Ardakani, M.; Romualdi, C.; Sales, G.; Barbie, D. A.; Boehm, J. S.; Hahn, W. C.; Mesirov, J. P.; Tamayo, P.

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Citation: Kim, J. W., O. B. Botvinnik, O. Abudayyeh, C. Birger, J. Rosenbluh, Y. Shrestha, M. E. Abazeed, et al. 2016. “Characterizing genomic alterations in cancer by complementary functional associations.” Nature biotechnology 34 (5): 539-546. doi:10.1038/nbt.3527. http://dx.doi.org/10.1038/nbt.3527.
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Abstract: Systematic efforts to sequence the cancer genome have identified large numbers of relevant mutations and copy number alterations in human cancers; however, elucidating their functional consequences, and their interactions to drive or maintain oncogenic states, is still a significant challenge. Here we introduce REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene-dependency of oncogenic pathways or the sensitivity to a drug treatment. We use REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.
Published Version: doi:10.1038/nbt.3527
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868596/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408333
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