G-protein coupled receptor expression patterns in medulloblastoma subgroups: identifying and exploiting molecular targets

Genome-wide association studies have identified several subgroups of medulloblastoma; however, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Group 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. 1 Chapter II, Section I is published in Acta Nueropathologica Communications with the following citation: Whittier KL, Boese EA, Gibson-Corley KN, Kirby PA, Darbro BW, Qian Q, Ingram WJ, Robertson T, Remke M, Taylor MD, O’Dorisio MS.. “G-protein coupled receptor expression patterns delineate medulloblastoma subgroups.” 2013; Acta Neuropath Comm 1(1):66.