OMICS AND PROGNSTIC MARKERS

Neuro-Oncology 15:iii136 – iii155, 2013. doi:10.1093/neuonc/not183 NEURO-ONCOLOGY 2013 WFNO-SNO Abstracts OMICS AND PROGNSTIC MARKERS Although histopathological diagnosis is essential in decision of therapeutic strategy for gliomas, sometimes the tumors diagnosed in one histological entity show thoroughly different clinical courses. This phenomenon is believed to be due primarily to the presence of the genetic subgroup. In fact, relationship between treatment response and certain genetic characteristics is indicated (e.g. better chemosensitivity in glioma with losses of 1p/19q (21p/19q)). It is highly likely that genetic classification of glioma is useful to select the adjuvant treatment. Additionally, gain of 7q (+7q) and 21p/19q are early events in 2 distinct tumor lineages, astrocytic tumors and oligodendroglial tumors, respectively, and these tumors obtain additional genetic aberration (29p, 10q) with tumor progression. On the other hand, concerning the tumors without +7q or 21p/19q, little is known about clinically important genetic aberration. Therefore the study on such tumors could provide useful information for the prognosis prediction and the determination of treatment strategy. METHODS: We selected 39 cases of gliomas without +7q or 21p/19q from 200 adult supratentorial glioma cases surgically treated and analyzed chromosomal DNA copy number aberrations (CNAs) by comparative genomic hybridization (CGH) from 2005 to 2012. We correlated clinical features of these tumors with histological characteristics, CNAs and IDH1 status. RESULTS: The clinical course of gliomas without +7q or 21p/19q was not correlated with additional genetic aberration of -9p or 10q, which have been known as genetic markers for poor prognosis, and absence of +7q or 21p/ 19q was maintained at the time of recurrence. The tumors without +7q or 21p/19q showed relatively favorable prognosis although mutation of IDH1 was infrequent in these tumors (35.8 %). CONCLUSION: The gliomas without +7q or 21p/19q have clinical features distinct from the +7q and 21p/19q gliomas. Prognostic markers for each subgroups could help establish therapeutic strategy against the tumor. OM-002. MOLECULAR CHARACTERIZATION OF 11p-DELETED DIFFUSE LOW-GRADE GLIOMAS Agusti Alentorn1, Yannick Marie2, Sylvie Poggioli1, Hussa Alshehhi3, Blandine Boisselier1, Catherine Carpentier1, Karima Mokhtari3, Laurent Capelle4, Dominique Figarella-Branger5, Khê Hoang-Xuan1,6, Marc Sanson1,6, Jean-Yves Delattre1,6, and Ahmed Idbaih1,6; 1Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière, INSERM UMRS 975/CNRS UMR 7225/UPMC, ICM, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 2Genotyping and sequencing platform, ICM, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 3Groupe Hospitalier Pitié-Salpêtrière, Department of Neuropathology, Paris, France; 4Groupe Hospitalier Pitié-Salpêtrière, Department of Neurosurgery, Paris, France; 5 INSERM, UMR 911, Medical School, Aix-Marseille University, Marseille, France; 6Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology Mazarin, Paris, France Diffuse low grade gliomas (LGG) form a heterogeneous subgroup of glial tumors. Over the last years, several genetic and genomic alterations, with clinical and biological relevancies, have been identified in LGG: (i) 1p/19q co-deletion and (ii) recurrent mutations in IDH1/IDH2, ATRX, TP53, CIC and FUBP1 genes. In a previous study, we have identified a subgroup of non 1p/19q-codeleted LGG exhibiting 11p deletion, astrocytic phenotype and poor prognosis. In order to better characterize 11p-deleted LGG, we have OM-003. MOLECULAR FEATURES OF ADULT PATIENTS WITH GANGLIOGLIOMAS Shlomit Yust-Katz, Mark Anderson, Adriana Olar, Agda Eterovic, Nader Ezzeddine, Ken Chen, Hao Zhao, Gregory Fuller, Kenneth Aldape, and John de Groot; The UT MD Anderson Cancer Center, Houston, TX, USA BACKGROUND: Gangliogliomas represent less than 1% of primary brain tumors in adults. Little is known regarding molecular characteristics and their potential impact on patient outcomes. METHODS: In this IRB approved retrospective study, our neuro-oncology longitudinal database was screened for patients with gangliogliomas from 1992-2012. 69 adult patients (age . 18) were identified, of whom 29 patients had 32 tissue samples eligible for analysis. DNA was extracted from archival tumors and hot spot mutation testing was performed using targeted ultradeep exome sequencing of approximately 200 cancer related genes in the research environment; copy number, loss of heterozygosity and intratumoral heterogeneity were assessed. RESULTS: 24 (83%) patients presented with low grade gangliogliomas, 5 (17%) presented with high grade gangliogliomas. The median age at diagnosis was 27 years (18-65). The median KPS at presentation was 100 (70-100). Patients underwent gross total resection (16, 55%), subtotal resection (11, 38%), or biopsy (2, 7%). The median overall survival for all patients was 4.1 years. 6 of the patients with low grade gangliogliomas had malignant transformation to a higher grade. The median overall survival for those patients was 1.1 years. Tissue submitted for analysis represented 17 low grade and 9 high grade samples from unique patients. In 3 patients, tissue was submitted from an initial low grade and then a recurrent high grade sample. Complete molecular profiling data will be presented. CONCLUSIONS: While gangliogliomas have an excellent prognosis, some patients have more aggressive tumors especially those undergoing malignant transformation. Molecular characterization of low and high grade gangliogliomas will provide additional insight into the biologic behavior of these tumors. OM-004. CLONAL EXPANSIONS AND EVOLVING SUBPOPULATIONS IN GLIOBLASTOMA MULTIFORME Noemi Andor1,,3, Julie Harness1,4, Sandra Gomez Lopez1,4, Tang Ling Fung6,7, Hans W. Mewes2,3, and Claudia Petritsch1,4; 1Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; 2 Helmholtz Zentrum München, Neuherberg, Germany; 3Ludwig Maximilians Universität München, München, Germany; 4Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, USA; 5Brain Tumor Research Center, UCSF, San Francisco, CA, USA; 6Institute of Human Genetics, UCSF, San Francisco, CA, USA; 7Cardiovascular Research Institute, UCSF, San Francisco, CA, USA MOTIVATION: Cancers are thought to arise from a single cell that has acquired a mutation that provides a survival benefit. The clonal evolution model indicates that cells with initiating mutations proceed to acquire additional mutations. Growth advantageous mutations cause the expansion of cancer cell subclones, resulting in tumors that consist of multiple, genetically distinct subpopulations. This genetic heterogeneity is thought to increase a tumor’s survival chances when confronted with therapies by providing a diverse repertoire of phenotypic responses. A systematic approach to (...truncated)