title: Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.
abstract: Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor.
authors.affiliation: Authors' Affiliations: Division of Neuropathology, Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Histopathology, Neural Development Unit, and UCL Genomics, UCL Institute of Child Health, Great Ormond Street Hospital, London; and Children's Brain Tumour Research Centre, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Nico V
authors.initials: NV
authors.lastname: Henriquez
authors.forename: Tim
authors.initials: T
authors.lastname: Forshew
authors.forename: Ruth
authors.initials: R
authors.lastname: Tatevossian
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.forename: Angela
authors.initials: A
authors.lastname: Richard-Loendt
authors.forename: Hazel
authors.initials: H
authors.lastname: Rogers
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.forename: Pablo Garcia
authors.initials: PG
authors.lastname: Reitboeck
authors.forename: Kerra
authors.initials: K
authors.lastname: Pearce
authors.forename: Denise
authors.initials: D
authors.lastname: Sheer
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D019070:Cell Lineage; D020869:Gene Expression Profiling; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010641:Phenotype; D011506:Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated; D060888:Real-Time Polymerase Chain Reaction; D016160:Retinoblastoma Protein / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D012333:RNA, Messenger; D022661:RNA, Untranslated; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse