title: Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes.
abstract: In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cusulin
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Chesnelong
authors.affiliation: British Columbia Cancer Agency Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Bose
authors.affiliation: British Columbia Cancer Agency Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Misha
authors.initials: M
authors.lastname: Bilenky
authors.affiliation: Department of Mathematics and Statistics, University of Calgary, Calgary, AB T2N 4N1, Canada; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Kopciuk
authors.affiliation: Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chan
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Cairncross
authors.affiliation: British Columbia Cancer Agency Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Jones
authors.affiliation: British Columbia Cancer Agency Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: H Artee
authors.initials: HA
authors.lastname: Luchman
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: weiss@ucalgary.ca.
authors.forename: Samuel
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D018740:Genetic Heterogeneity; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*; D059467:Transcriptome / Q000235:genetics; D023041:Xenograft Model Antitumor Assays