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Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

2017; American Association for Cancer Research; Volume: 77; Issue: 16 Linguagem: Inglês

10.1158/0008-5472.can-16-2550

1538-7445

Emmy D.G. Fleuren, Myrella Vlenterie, Winette T.A. van der Graaf, Melissa H.S. Hillebrandt-Roeffen, James Blackburn, Xiuquan Ma, Howard Chan, Mandy C. Magias, Anke van Erp, Laurens van Houdt, Sabri A.S. Cebeci, Amy van de Ven, Uta Flucke, Erin E. Heyer, David M. Thomas, Christopher J. Lord, Kieren D. Marini, Vijesh Vaghjiani, Tim R. Mercer, Jason E. Cain, Jianmin Wu, Yvonne M.H. Versleijen‐Jonkers, Roger J. Daly,

Peptidase Inhibition and Analysis

Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases. ALK was identified as a novel driver in the Aska-SS synovial sarcoma (SS) cell line via expression of an ALK variant with a large extracellular domain deletion (ALK