title: Impact of genetic targets on primary brain tumor therapy: what's ready for prime time?
abstract: Primary brain tumors constitute a substantial public health problem with 66,290 cases diagnosed in the US in 2012, and 13,700 deaths recorded. With discovery of genetic factors associated with specific brain tumor subtypes, the goal of therapy is changing from treating a class of tumors to developing individualized therapies catering to the molecular composition of the actual tumor. For oligodendrogliomas, the loss of 1p/19q due to an unbalanced translocation improves both survival and the response to therapy, and is thus both a prognostic and a predictive marker. Several additional genetic alterations such as EGFR amplification, MGMT methylation, PDGFR activation, and 9p and 10q loss, have improved our understanding of the characteristics of these tumors and may help guide therapy in the future. For astrocytic tumors, MGMT is associated with a better prognosis and an improved response to temozolomide, and for all glial tumors, mutations in the IDH1 gene are possibly the most potent of good prognostic markers. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the "triple negative" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. Newer markers, such as CD 133, require additional investigation to determine their prognostic and predictive utility. In medulloblastomas, markers of WNT activation, MYCC/MCYN amplification, and TrkC expression levels are reliable prognostic indicators, but do not yet drive specific treatment selection. Many other proposed markers, such as 17q gain, TP53 mutations, and hMOF protein expression show promise, but are not yet ready for prime time. In this chapter, we focus on the markers that have shown convincing prognostic, predictive, and diagnostic value, and discuss potential markers that are being currently being intensively investigated. We also discuss serum profiling of tumors in an effort to discover additional potential markers.
authors.affiliation: Department of Neurosurgery, Penn State College of Medicine, Hershey Medical Center, EC 1001, 30 Hope Drive, Hershey, PA 17033, USA. ozz101@gmail.com
authors.forename: O
authors.initials: O
authors.lastname: Zalatimo
authors.forename: C M
authors.initials: CM
authors.lastname: Zoccoli
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: C L
authors.initials: CL
authors.lastname: Weston
authors.forename: M
authors.initials: M
authors.lastname: Glantz
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002872:Chromosome Deletion; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes