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      Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.

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          Abstract

          Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRalpha and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          0092-8674
          0092-8674
          Dec 14 2007
          : 131
          : 6
          Affiliations
          [1 ] Cell Signaling Technology, 3 Trask Lane, Danvers, MA 01923, USA.
          Article
          S0092-8674(07)01522-X
          10.1016/j.cell.2007.11.025
          18083107
          fdc0b4e4-7622-4c00-98e2-31a5ecf4beb8
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