Edward Kastenhuber, BSE

Research Technician

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University of Pittsburgh

Recent large-scale genomic analyses have identified a defined set of molecular pathways whose dysregulation appears to underlie the pathogenesis of this tumor. By alternatively implicating distinct molecular networks, such as the EGFR and PDGFR signaling cascades, in gliomagenesis, these studies have also advanced the notion of discrete glioma subclasses, each driven by different sets of genomic abnormalities, that would presumably exhibit varying degrees of response to currently available targeted therapies. The ability to rapidly and effectively stratify patients with malignant glioma into molecular subgroups would therefore benefit the design and execution of drug trials. To this end, we are developing a set of bioassays designed to obtain accurate molecular information from formalin-fixed paraffin-embedded (FFPE) tissue blocks, the only tumor material available for the majority of patients. Our methods include mutational analysis of glioma-relevant genes using both RT-PCR and sequencing platforms, focused copy number analysis, immunohistochemical profiling, and mRNA/miRNA biomarker development. Through this analysis, we hope to provide support for prospectively stratified clinical trials and a pipeline for the molecular evaluation of large paraffin-embedded tumor sets.