Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target

• DOI: 10.1073/pnas.0608396103
• Publication Date: 2006-11-08T03:59:07Z
• Authors: S. Horvath; B. Zhang; M. Carlson; K. V. Lu; S. Zhu; R. M. Felciano; M. F. Laurance; W. Zhao; S. Qi; Z. Chen; Y. Lee; A. C. Scheck; L. M. Liau; H. Wu; D. H. Geschwind; P. G. Febbo; H. I. Kornblum; T. F. Cloughesy; S. F. Nelson; P. S. Mischel
• Keywords: Oncogene Proteins; 0303 health sciences; Gene Expression Profiling; ELAV-Like Protein 2; Breast Neoplasms; Nerve Tissue Proteins; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; ELAV Proteins; Animals; Humans; RNA Interference; Glioblastoma; Cells, Cultured; Signal Transduction

Glioblastoma is the most common primary malignant brain tumor of adults and one lethal all cancers. Patients with this disease have a median survival 15 months from time diagnosis despite surgery, radiation, chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit molecularly targeted therapies. Here, we address compelling need for identification new molecular targets. Leveraging global gene expression data two independent sets clinical samples (n = 55 n 65), identify coexpression module in also present breast cancer significantly overlaps "metasignature" undifferentiated cancer. Studies an isogenic model system demonstrate downstream mutant epidermal growth factor receptor, EGFRvIII, it can be inhibited by receptor tyrosine kinase inhibitor Erlotinib. We ASPM (abnormal spindle-like microcephaly associated) as key within its overexpression relative to normal (or body tissues). Finally, show inhibition siRNA-mediated knockdown inhibits cell proliferation neural stem proliferation, supporting potential target glioblastoma. Our weighted network analysis provides blueprint leveraging genomic control networks targets glioblastoma, principle eluted our work applied other