We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

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This study was a retrospective review of 3,806 patients who underwent anterior cervical spine surgery with multi-modality neurophysiological monitoring consisting of transcranial electric motor evoked potentials, somatosensory evoked potentials and spontaneous electromyography between 1999-2003. The objectives of this study were twofold: (1) to evaluate the role of transcranial electric motor evoked potential tceMEP and ulnar nerve somatosensory evoked potential (SSEP) monitoring for identifying impending position-related stretch brachial plexopathy, peripheral nerve entrapment/compression or spinal cord compression and (2) to estimate the point-prevalence of impending neurologic injury secondary to surgical positioning effects. Sixty-nine of 3,806 patients (1.8% showed intraoperative evidence of impending neurologic injury secondary to positioning, prompting interventional repositioning of the patient. The brachial plexus was the site of evolving injury in 65% of these 69 cases. Impending brachial plexopathy was most commonly noted immediately following shoulder taping and the application of counter-traction. Brachial plexus stretch upon neck extension for optimal surgical access and visualization was second in frequency-of-occurrence. Evolving traction injury to the ulnar nerve attributed to tightly-wrapped or malpositioned arms was observed in 16% of alerted cases, whereas evolving spinal cord injury following neck extension accounted for an additional 19%. This study highlights the role of tceMEP and ulnar nerve SSEP monitoring for detecting emerging peripheral nerve injury secondary to positioning in preparation for and during anterior cervical spine surgery.

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