title: Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
abstract: Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.
authors.affiliation: Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080, USA. hsp@gene.com
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Phillips
authors.forename: Samir
authors.initials: S
authors.lastname: Kharbanda
authors.forename: Ruihuan
authors.initials: R
authors.lastname: Chen
authors.forename: William F
authors.initials: WF
authors.lastname: Forrest
authors.forename: Robert H
authors.initials: RH
authors.lastname: Soriano
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wu
authors.forename: Anjan
authors.initials: A
authors.lastname: Misra
authors.forename: Janice M
authors.initials: JM
authors.lastname: Nigro
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Liliana
authors.initials: L
authors.lastname: Soroceanu
authors.forename: P Mickey
authors.initials: PM
authors.lastname: Williams
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: Burt G
authors.initials: BG
authors.lastname: Feuerstein
authors.forename: Ken
authors.initials: K
authors.lastname: Aldape
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001921:Brain / Q000254:growth & development; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C496666:DLL3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051059:PTEN Phosphohydrolase