title: Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis.
abstract: BACKGROUND
  The subventricular zone (SVZ) has been implicated in the pathogenesis of glioblastoma. Whether molecular subtypes of glioblastoma arise from unique niches of the brain relative to the SVZ remains largely unknown. Here, we tested whether these subtypes of glioblastoma occupy distinct regions of the cerebrum and examined glioblastoma localization in relation to the SVZ.
  
  
  METHODS
  Pre-operative MR images from 217 glioblastoma patients from The Cancer Imaging Archive were segmented automatically into contrast enhancing (CE) tumor volumes using Iterative Probabilistic Voxel Labeling (IPVL). Probabilistic maps of tumor location were generated for each subtype and distances were calculated from the centroid of CE tumor volumes to the SVZ. Glioblastomas that arose in a Genetically Modified Murine Model (GEMM) model were also analyzed with regard to SVZ distance and molecular subtype.
  
  
  RESULTS
  Classical and mesenchymal glioblastomas were more diffusely distributed and located farther from the SVZ. In contrast, proneural and neural glioblastomas were more likely to be located in closer proximity to the SVZ. Moreover, in a GFAP-CreER; PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1-/- GEMM model of glioblastoma where tumor can spontaneously arise in different regions of the cerebrum, tumors that arose near the SVZ were more likely to be of proneural subtype (p < 0.0001).
  
  
  CONCLUSIONS
  Glioblastoma subtypes occupy different regions of the brain and vary in proximity to the SVZ. These findings harbor implications pertaining to the pathogenesis of glioblastoma subtypes.
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Steed
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Treiber
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.|Weill-Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Kunal
authors.initials: K
authors.lastname: Patel
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Valya
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Merk
authors.affiliation: Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Smith
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Bob S
authors.initials: BS
authors.lastname: Carter
authors.affiliation: Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA.|Department of Radiology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Lionel M L
authors.initials: LM
authors.lastname: Chow
authors.affiliation: Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Clark C
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D020547:Lateral Ventricles / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: MR imaging; automatic tumor segmentation; glioblastoma; subtypes; subventricular zone