Abstracts vi110 NEURO-ONCOLOGY • NOVEMBER 2016 IHC scores refect the dense cellularity of these tumors. This is consistent with our previous advanced MR imaging fndings where the ADC of pure astrocytomas was signifcantly lower than that of oligodendrogliomas and mixed tumors, and mixed GBMs had a signifcantly lower ADC than con- ventional ones. The high IHC scores (AS=7) seen in recurrent GBM samples are likely due to overexpression of ASAH1 following radiation therapy. Our results support a biological distinction between astrocytomas and oligoden- drogliomas, and a biological agreement between oligodendrogliomas and oligoastrocytomas, corroborating previous fndings that mixed gliomas may not represent a separate glioma group, but rather a subtype of oligodendro- gliomas. Further tissue analysis on more specimens is underway. CONCLU- SION: Acid ceramidase shows great potential as a supplemental biomarker in glioma characterization. MPTH-20. PREOPERATIVE SERUM microRNA PROFILING AS A DIAGNOSTIC TOOL IN GLIOMA Andrew Morokoff 1,2 , Iwan Bennett 1 , Lucy Paradiso 1 , Rod Luwor 1 , Michael Wong 1 , Rachel Koldej 2 , Jason Li 1 , Chenkai Ma 1 , Kate Drummond 2 , Stanley Stylli 2 , Andrew Kaye 1,2 and Tali Siegal 3 ; 1 University of Melbourne, Melbourne, Australia, 2 Royal Melbourne Hospital, Melbourne, Australia, 3 Center for Neuro-Oncology, Oncology Institute, Davidoff Center, Rabin Medical Center, Petah-Tikva, Israel BACKGROUND: Current diagnosis of glioma is based on clinical sus- picion, magnetic resonance imaging (MRI) and ultimately surgical biopsy based on WHO criteria for neuropathology. Blood sampling for circulating assessment of biomarkers is a potentially valuable method that could supple- ment diagnostic criteria by providing pre-operative molecular information. We previously showed that miR-10b and miR-21 were signifcantly upregu- lated in untreated high-grade glioma patients compared to healthy controls. We hypothesized that largescale miRNA profling could improve diagnos- tic discrimination across all grades of glioma. METHODS: Pre-operative serum samples were collected from 91 glioma patients (45 GBM, 46 low grade glioma) presenting to the Royal Melbourne Hospital between 2009 and 2014, and compared to 20 healthy controls. Profling of 800 microR- NAs was performed by Nanostring ® v.3 analysis of isolated total serum RNA. Statistical output and heatmaps were generated using nSolver and R packages. RESULTS: miRNA profles differed signifcantly between GBM, LGG and healthy controls. Highly differentially upregulated miRs included miR-21, miR-29a and miR-363. miR-21 and miR-29a were signifcantly associated with overall survival. A 19-miRNA gene classifer incorporating miRs with p<0.01 and log-fold change >0.5 in either direction was able to discriminate strongly between GBM and LGG. CONCLUSIONS: Lar- gescale profling of miRNA expression levels in serum shows promise for discovery of diagnostic and prognostic circulating biomarkers. These results require validation in prospective data sets. MPTH-21. MOLECULAR CHARACTERIZATION REVEALS NF1 LOSS AND FGFR1 ACTIVATING MUTATIONS IN PEDIATRIC SPINAL OLIGODENDROGLIOMA Amy K. Bruzek 1 , Andrew Zureick 1 , Sriram Venneti 2 , Paul McKeever 1 , Hugh J.L. Garton 1 , Patricia Robertson 1 , Rajen Mody 1 and Carl Koschmann 1 ; 1 University of Michigan, Ann Arbor, MI, USA, 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA Spinal anaplastic oligodendroglioma is a rare and aggressive tumor. Despite maximal treatment with surgical resection, radiation therapy, and chemotherapy, survival is less than 50% at 5 years. Spinal oligodendro- glioma is generally seen in older patients, but it has also been reported in children. Little is known of the molecular drivers of this tumor. We pre- sent a nine-year-old girl who was diagnosed at age three with an anaplastic oligodendroglioma of the cervical spine. She underwent subtotal resection followed by cyclic temozolomide for 16 months. She developed local recur- rent disease at age eight and again underwent subtotal resection. At recur- rence, tumor pathology showed Grade III oligodendroglioma, 1p/19q co-deletion negative, MGMT unmethylated, IDH mutation negative. We performed exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing on her recurrent tumor. Sequencing revealed a point mutation and three small deletions, all somatic, in neurofbromin 1 (NF1). She had no evidence of germline NF1 alterations, skin lesions, or a family history suggestive of familial NF1. We also observed two activating mis- sense somatic mutations adjacent to tyrosine phosphorylation sites Y653 and Y654 on fbroblast growth factor receptor 1 (FGFR1). After resection, she underwent focal proton irradiation, and subsequently developed acute radiation necrosis, which has responded well to treatment with steroids and bevacizumab. Results of her tumor sequencing were discussed in a CNS pre- cision medicine tumor board teleconferenced with clinicians at multiple chil- dren’s hospitals, which made recommendation to consider adjuvant therapy with an FGFR inhibitor (for FGFR1 mutations) and/or a MEK inhibitor (for NF1 loss-of-function). We will consider these therapies with family after fur- ther resolution of her radiation necrosis. In summary, we provide genomic data on a case of pediatric spinal anaplastic oligodendroglioma. This data allowed us to examine potential personalized therapies for this patient, and expose molecular drivers that may be involved in similar cases. MPTH-22. SERUM 2-HYDROXYGLUTARATE (2HG) LEVELS ARE CORRELATED WITH TISSUE 2HG LEVELS IN ISOCITRATE DEHYDROGENASE 1 AND 2 GENES (IDH1/2)-MUTATED GLIOMAS BUT NOT IN IDH1/2-WILDTYPE GLIOMAS Makoto Ohno 1 , Hiroaki Aikawa 2,3 , Mitsuhiro Hayashi 3 , Yuko Matsushita 1 , Yasuji Miyakita 1 , Masamichi Takahashi 1 , Shunichiro Miki 1 , Yosuke Kitagawa 1 , Takahiro Yamauchi 1 , Koichi Ichimura 4 , Akinobu Hamada 3 and Yoshitaka Narita 1 ; 1 Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan, 2 Division of Clinical Pharmacology & Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo, Japan, 3 Division of Clinical Pharmacology, National Cancer Center Research Institute, Tokyo, Japan, 4 Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan Mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1/2) frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDH1/2 proteins gain a new ability to produce the oncometabolite 2-hydroxyglutar- ate (2HG), however, the clinical impact of 2HG is not clear. In this study, we analyzed 2HG levels in both serum and tumor tissue and evaluated the role of 2HG in diffuse gliomas. We measured 2HG concentrations in 123 serums and in 78 tumor tissues by using liquid chromatography-tandem mass spectrometry method. IDH1/2 mutations status were determined by direct sequencing and/or immunohistochemistry. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylations were analyzed using pyrosequencing and defned the mean level of methylation at the 16 CpG sites.Serum levels of 2HG in 42 patients with IDH-Mut tumors did not dif- fer from those in 81 patients with IDH-WT tumors (median: 19.9 ng/mL for IDH-Mut vs 22.8 ng/mL for IDH-WT, p=0.86), however, tissue levels of 2HG in 28 patients with IDH-Mut tumors were signifcantly higher than those in 50 patients with IDH-WT tumors (median: 4.9 ug/mg for IDH- Mut vs 0.09 ug/mg for IDH-WT, p<0.0001). In 28 patients with IDH-Mut tumors, serum levels of 2HG were signifcantly correlated with tissue levels of 2HG (R 2  = 0.39, p=0.0004), but in 50 patients with IDH-WT tumors, serum and tissue levels of 2HG did not show the relationship (R 2  = 0.067, p=0.070). Tissue levels of 2HG showed a signifcant correlation with MGMT promoter methylations (R 2 = 0.15, p=0.0024).Our results suggest that tumor-derived 2HG is released in serum in the patients with IDH1/2 Mut tumors, however, their amounts are too small to detect the difference of serum 2HG levels in between patients with IDH-Mut and IDH-WT tumors. Accumulation of 2HG in tumor tissue may have an impact on MGMT pro- moter methylations. MPTH-23. LONG-TERM SURVIVAL WITH GLIOBLASTOMA IN THE ELDERLY Guido Reifenberger 1 , Martin Sill 2 , Bettina Hentschel 3 , Jörg Felsberg 4 , David T. W. Jones 5 , Dorothee Gramatzki 6 , Kerstin Kaulich 7 , Joerg-Christian Tonn 8 , Ulrich Herrlinger 9 , Gabriele Schackert 10 , Manfred Westphal 11 , Michael Sabel 12 , David Capper 13 , Rajiv Kumar 14 , Kari Hemminki 14 , Torsten Pietsch 15 , Markus Loeffer 3 , Stefan M. Pfster 2 ,Andreas von Deimling 16 and Michael Weller 6 ; 1 Department of Neuropathology, Heinrich Heine University, Düsseldorf, Germany, 2 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 3 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany, 4 Dept. of Neuropathology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany, 5 German Cancer Consortium (DKTK), Heidelberg, Germany, 6 Department of Neurology, University Hospital Zurich, Zurich, Switzerland, 7 Department of Neuropathology, Heinrich Heine University, Duesseldorf, Germany, 8 Department of Neurosurgery, Ludwig-Maximilians-University Munich, Munich, Germany, 9 Division of Clinical Neurooncology, Department of Neurology; University of Bonn Medical Center, Bonn, Germany, 10 Department of Neurosurgery, Technical University Dresden, Dresden, Germany, 11 Department of Neurosurgery, University of Hamburg, Hamburg, Germany, 12 Department of Neurosurgery, Heinrich Heine University, Duesseldorf, Germany, 13 Department of Neuropathology, University of Heidelberg, Heidelberg, Germany, 14 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 15 Department of Neuropathology, University of Bonn, Bonn, Germany, 16 Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany BACKGROUND: The median survival of patients with glioblastoma is in the range of 12-18 months in population-based studies. A minority of affected patients, however, achieve long-term survival (LTS), arbitrarily defned as survival of more than 36 months or more than 60 months after diagnosis. Prognostic factors associated with LTS include younger age, gross total tumor resection, O6-methylguanine DNA methyltransferase Downloaded from https://academic.oup.com/neuro-oncology/article/18/suppl_6/vi110/2542709 by guest on 30 September 2021