Identification of activated TrkB as a potential oncogenic tyrosine kinase by an in vivo screen. (A) Top panel, schematic structure of tyrosine kinase–TEL (TK-TEL) library; bottom panel, schematic flow chart of the in vivo tumorigenesis assay used to screen the TK-TEL library for transformation of Ink4a^−/−/Arf^−/− astrocytes in mice. (B) Schematic structure of the QKI-NTRK2 fusion protein. (C) Kaplan–Meier survival curves of mice bearing intracranially implanted Ink4a^−/−/Arf^−/−/QKI-NTRK2 (blue line, n = 4), Ink4a^−/−/Arf^−/−/NTRK2-TEL (red line, n = 4), or Ink4a^−/−/Arf^−/−/Vector (black line, n = 2) astrocytes. (D) Hematoxylin and eosin staining and IHC analysis of GFAP (glioma cell marker), Sox2 (neural stem cell marker), and Ki67 (proliferative marker) in the indicated astrocytomas. Scale bar, 50 μm. Bar graph represents quantification of Ki67 in tumors (mean ± SD).