Molecular heterogeneity of glioblastomas: does location matter?
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Emilie Denicolaï1, Emeline Tabouret1,2, Carole Colin1, Philippe Metellus3, Isabelle Nanni4, Celine Boucard2, Aurélie Tchoghandjian1, David Meyronet5, Nathalie Baeza-Kallee1, Olivier Chinot1,2, Dominique Figarella-Branger1,6
1Aix-Marseille University, CRO2 UMR 911, Inserm UMR_S 911, Marseille, 13385, France
2AP-HM, Timone Hospital, Department of Neuro-Oncology, Marseille, 13385, France
3AP-HM, Timone Hospital, Department of Neuro-Surgery, Marseille, 13385, France
4AP-HM, North Hospital, Transfer Laboratory, Marseille, 13915, France
5Hospices Civils de Lyon, Centre de Pathologie et de Neuropathologie Est, Lyon, 69677, France
6AP-HM, Timone Hospital, Department of Anatomopathology, Marseille, 13385, France
Dominique Figarella-Branger, e-mail: [email protected]
Keywords: tumor location, glioblastoma, mesenchymal profile, proneural profile
Received: July 01, 2015 Accepted: November 20, 2015 Published: November 30, 2015
Glioblastomas in adults are highly heterogeneous tumors that can develop throughout the brain. To date no predictive-location marker has been identified. We previously derived two glioblastoma cell lines from cortical and periventricular locations and demonstrated distinct transcriptomic profiles. Based on these preliminary results, the aim of this study was to correlate glioblastoma locations with the expression of ten selected genes (VEGFC, FLT4, MET, HGF, CHI3L1, PROM1, NOTCH1, DLL3, PDGFRA, BCAN). Fifty nine patients with newly diagnosed glioblastomas were retrospectively included. Tumors were classified into cortical and periventricular locations, which were subsequently segregated according to cerebral lobes involved: cortical fronto-parietal (C-FP), cortical temporal (C-T), periventricular fronto-parietal (PV-FP), periventricular temporal (PV-T), and periventricular occipital (PV-O). Gene expression levels were determined using RT-qPCR. Compared to cortical glioblastomas, periventricular glioblastomas were characterized by a higher expression of two mesenchymal genes, VEGFC (p = 0.001) and HGF (p = 0.001). Among cortical locations, gene expressions were homogeneous. In contrast, periventricular locations exhibited distinct expression profiles. PV-T tumors were associated with higher expression of two proneural and cancer stem cell genes, NOTCH1 (p = 0.028) and PROM1 (p = 0.033) while PV-FP tumors were characterized by high expression of a mesenchymal gene, CHI3L1 (p = 0.006). Protein expression of NOTCH1 was correlated with RNA expression levels. PV-O glioblastomas were associated with lower expression of VEGFC (p = 0.032) than other periventricular locations, whereas MET overexpression remained exceptional. These data suggest a differential gene expression profile according to initial glioblastoma location.
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