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Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

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Abstract

Glioblastoma (GB) is the most frequent and aggressive type of primary brain tumor. Recurrences are mostly located at the margin of the resection cavity in the peritumoral brain zone (PBZ). Although it is widely believed that infiltrative tumor cells in this zone are responsible for GB recurrence, few studies have examined this zone. In this study, we analyzed PBZ left after surgery with a variety of techniques including radiology, histopathology, flow cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The resulting PBZ profiles were compared with those of the GB tumor zone and normal brain samples to identify characteristics specific to the PBZ. We found that tumor cell infiltration detected by standard histological analysis was present in almost one third of PBZ taken from an area that was considered normal both on standard MRI and by the neurosurgeon under an operating microscope. The panel of techniques used in this study show that the PBZ, similar to the tumor zone itself, is characterized by substantial inter-patient heterogeneity, which makes it difficult to identify representative markers. Nevertheless, we identified specific alterations in the PBZ such as the presence of selected tumor clones and stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is a growing field of interest and this region needs to be characterized further. This will facilitate the development of new, targeted therapies for patients with GB and the development of approaches to refine the per-operative evaluation of the PBZ to optimize the surgical resection of the tumor.

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Acknowledgments

We gratefully acknowledge the neurosurgeons, the radiologists and the neuropathologists at the University Hospitals of Angers, Rennes, Poitiers, Brest, and Tours for supplying us with GB and PBZ tissue samples. We also thank the members of the glioma network of the Cancéropole Grand Ouest and Agnès Chassevent for providing facilities. This work was supported by the Cancéropôle Grand Ouest and the Institut National du Cancer (INCa). The first author of the study (J.-M.L.) received grants from the Société Française de Neuro-Chirurgie (SFNC) and from the Institut National de la Santé et de la Recherche Médicale (INSERM).

Conflicts of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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Authors and Affiliations

  1. Département de Neurochirurgie, Centre Hospitalier Universitaire d’Angers, 4 rue Larrey, 49933, Angers Cedex 09, France

    Jean-Michel Lemée, Anne Clavreul & Philippe Menei

  2. INSERM UMR-1066, Micro- et Nanomédecine Biomimétiques (MINT), 4 rue Larrey, 49933, Angers Cedex 09, France

    Jean-Michel Lemée, Anne Clavreul, Audrey Rousseau & Philippe Menei

  3. UMR 6290 CNRS “Génomique fonctionnelle intégrée et biomarqueurs”, Université Rennes 1, 35043, Rennes, France

    Marc Aubry, Marie de Tayrac & Jean Mosser

  4. Proteomic Core Facility BiogenOuest, IRSET, Inserm U1085, Campus de Beaulieu, 35042, Rennes, France

    Emmanuelle Com

  5. Service de Génétique Moléculaire et Génomique CHU de Rennes - Hôpital Pontchaillou, 2 Rue Henri Le Guilloux, 35033, Rennes Cedex 9, France

    Marie de Tayrac & Jean Mosser

  6. PRISM, SFR Biosit, Université de Rennes 1, CNRS UMS 3480 - INSERM US 018, 35043, Rennes, France

    Pierre-Antoine Eliat

  7. Centre Régional de Lutte contre le Cancer Paul Papin, 2 rue Moll, 49000, Angers, France

    Cécile Henry

  8. Département de Pathologie Cellulaire et Tissulaire, Centre Hospitalo-universitaire d’Angers, 4 rue Larrey, 49933, Angers Cedex 09, France

    Audrey Rousseau

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  1. Jean-Michel Lemée
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  2. Anne Clavreul
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  9. Jean Mosser
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Correspondence to Philippe Menei.

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Lemée, JM., Clavreul, A., Aubry, M. et al. Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis. J Neurooncol 122, 53–61 (2015). https://doi.org/10.1007/s11060-014-1695-8

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  • DOI: https://doi.org/10.1007/s11060-014-1695-8

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