title: Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone.
abstract: Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance.
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Sara Gm
authors.initials: SG
authors.lastname: Piccirillo
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Spiteri
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sottoriva
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.|European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Anestis
authors.initials: A
authors.lastname: Touloumis
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Suzan
authors.initials: S
authors.lastname: Ber
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Price
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Heywood
authors.affiliation: Department of Oncology and the Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK.
authors.forename: Nicola-Jane
authors.initials: NJ
authors.lastname: Francis
authors.affiliation: Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Howarth
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Collins
authors.affiliation: Department of Oncology and the Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK.
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Venkitaraman
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Curtis
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Marioni
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.|Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004805:Ependyma / Q000473:pathology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology*