title: Comparative genomic and genetic analysis of glioblastoma-derived brain tumor-initiating cells and their parent tumors.
abstract: BACKGROUND
  Glioblastoma (GBM) is a fatal cancer that has eluded major therapeutic advances. Failure to make progress may reflect the absence of a human GBM model that could be used to test compounds for anti-GBM activity. In this respect, the development of brain tumor-initiating cell (BTIC) cultures is a step forward because BTICs appear to capture the molecular diversity of GBM better than traditional glioma cell lines. Here, we perform a comparative genomic and genetic analysis of BTICs and their parent tumors as preliminary evaluation of the BTIC model.
  
  
  METHODS
  We assessed single nucleotide polymorphisms (SNPs), genome-wide copy number variations (CNVs), gene expression patterns, and molecular subtypes of 11 established BTIC lines and matched parent tumors.
  
  
  RESULTS
  Although CNV differences were noted, BTICs retained the major genomic alterations characteristic of GBM. SNP patterns were similar between BTICs and tumors. Importantly, recurring SNP or CNV alterations specific to BTICs were not seen. Comparative gene expression analysis and molecular subtyping revealed differences between BTICs and GBMs. These differences formed the basis of a 63-gene expression signature that distinguished cells from tumors; differentially expressed genes primarily involved metabolic processes. We also derived a set of 73 similarly expressed genes; these genes were not associated with specific biological functions.
  
  
  CONCLUSIONS
  Although not identical, established BTIC lines preserve the core molecular alterations seen in their parent tumors, as well as the genomic hallmarks of GBM, without acquiring recurring BTIC-specific changes.
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Brad
authors.initials: B
authors.lastname: Davis
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Candice C
authors.initials: CC
authors.lastname: Poon
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: H Artee
authors.initials: HA
authors.lastname: Luchman
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Owen D
authors.initials: OD
authors.lastname: Stechishin
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Carly S
authors.initials: CS
authors.lastname: Pontifex
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: John J
authors.initials: JJ
authors.lastname: Kelly
authors.affiliation: Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada (B.D., Y. S.); Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., J.J.K.); Clark Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (C.C.P., C.S.P., W.W., J.J.K., M.D.B.); Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (H.A.L., O.D.S.).
authors.forename: Michael D
authors.initials: MD
authors.lastname: Blough
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D001323:Autoantibodies; C051951:antiglomerular basement membrane antibody
keywords: brain tumor-initiating cells; copy number variation; genetic analyses; genomic analyses; glioblastoma