Proteogenomic integration reveals therapeutic targets in breast cancer xenografts
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Author
Huang, Kuan-lin
Li, Shunqiang
Mertins, Philipp
Cao, Song
Gunawardena, Harsha P.
Ruggles, Kelly V.
Mani, D. R.
Clauser, Karl R.
Tanioka, Maki
Usary, Jerry
Kavuri, Shyam M.
Xie, Ling
Yoon, Christopher
Qiao, Jana W
Wrobel, John
Wyczalkowski, Matthew A.
Erdmann-Gilmore, Petra
Snider, Jacqueline E.
Hoog, Jeremy
Singh, Purba
Niu, Beifung
Guo, Zhanfang
Sun, Sam Qiancheng
Sanati, Souzan
Kawaler, Emily
Wang, Xuya
Scott, Adam
Ye, Kai
McLellan, Michael D.
Wendl, Michael C.
Malovannaya, Anna
Held, Jason M.
Fenyö, David
Kinsinger, Christopher R.
Mesri, Mehdi
Rodriguez, Henry
Davies, Sherri R.
Perou, Charles M.
Ma, Cynthia
Reid Townsend, R.
Chen, Xian
Carr, Steven A.
Ellis, Matthew J.
Ding, Li
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms14864Metadata
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Huang, K., S. Li, P. Mertins, S. Cao, H. P. Gunawardena, K. V. Ruggles, D. R. Mani, et al. 2017. “Proteogenomic integration reveals therapeutic targets in breast cancer xenografts.” Nature Communications 8 (1): 14864. doi:10.1038/ncomms14864. http://dx.doi.org/10.1038/ncomms14864.Abstract
Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379071/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630585
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