title: Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes.
abstract: A central question in glioblastoma multiforme (GBM) research is the identity of the tumor-initiating cell, and its contribution to the malignant phenotype and genomic state. We examine the potential of adult lineage-restricted progenitors to induce fully penetrant GBM using CNS progenitor-specific inducible Cre mice to mutate Nf1, Trp53, and Pten. We identify two phenotypically and molecularly distinct GBM subtypes governed by identical driver mutations. We demonstrate that the two subtypes arise from functionally independent pools of adult CNS progenitors. Despite histologic identity as GBM, these tumor types are separable based on the lineage of the tumor-initiating cell. These studies point to the cell of origin as a major determinant of GBM subtype diversity.
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: alcantas@mskcc.org.
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Alcantara Llaguno
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Zilai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Daochun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Euiseok
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Raisanen
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Burns
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Johnson
authors.affiliation: Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: paradal@mskcc.org.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D025542:Neurofibromin 1 / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D025542:Neurofibromin 1; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse