Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis

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 surv...

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Published in	Cancer cell Vol. 9; no. 3; pp. 157 - 173
Main Authors	Phillips, Heidi S., Kharbanda, Samir, Chen, Ruihuan, Forrest, William F., Soriano, Robert H., Wu, Thomas D., Misra, Anjan, Nigro, Janice M., Colman, Howard, Soroceanu, Liliana, Williams, P. Mickey, Modrusan, Zora, Feuerstein, Burt G., Aldape, Ken
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.03.2006
Subjects	Biomarkers, Tumor - analysis Brain - growth & development Brain Neoplasms - classification Brain Neoplasms - genetics Brain Neoplasms - pathology CELLCYCLE Disease Progression Gene Dosage Gene Expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Glioma - classification Glioma - genetics Glioma - pathology Humans In Situ Hybridization Intracellular Signaling Peptides and Proteins Membrane Proteins - biosynthesis Membrane Proteins - genetics Neoplasm Invasiveness - genetics Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Prognosis PTEN Phosphohydrolase - biosynthesis PTEN Phosphohydrolase - genetics CELLCYCLE
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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.
AbstractList	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. 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.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.
Author	Soroceanu, Liliana Modrusan, Zora Kharbanda, Samir Colman, Howard Soriano, Robert H. Forrest, William F. Misra, Anjan Aldape, Ken Nigro, Janice M. Phillips, Heidi S. Williams, P. Mickey Wu, Thomas D. Chen, Ruihuan Feuerstein, Burt G.
Author_xml	– sequence: 1 givenname: Heidi S. surname: Phillips fullname: Phillips, Heidi S. email: hsp@gene.com organization: Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080 – sequence: 2 givenname: Samir surname: Kharbanda fullname: Kharbanda, Samir organization: Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080 – sequence: 3 givenname: Ruihuan surname: Chen fullname: Chen, Ruihuan organization: Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080 – sequence: 4 givenname: William F. surname: Forrest fullname: Forrest, William F. organization: Department of Biostatistics, Genentech, Inc., South San Francisco, California 94080 – sequence: 5 givenname: Robert H. surname: Soriano fullname: Soriano, Robert H. organization: Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080 – sequence: 6 givenname: Thomas D. surname: Wu fullname: Wu, Thomas D. organization: Department of Bioinformatics, Genentech, Inc., South San Francisco, California 94080 – sequence: 7 givenname: Anjan surname: Misra fullname: Misra, Anjan organization: Brain Tumor Research Center, University of California, San Francisco, San Francisco, California 94143 – sequence: 8 givenname: Janice M. surname: Nigro fullname: Nigro, Janice M. organization: Brain Tumor Research Center, University of California, San Francisco, San Francisco, California 94143 – sequence: 9 givenname: Howard surname: Colman fullname: Colman, Howard organization: Department of Neuro-Oncology, M.D. Anderson Cancer Center, Houston, Texas 77030 – sequence: 10 givenname: Liliana surname: Soroceanu fullname: Soroceanu, Liliana organization: Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080 – sequence: 11 givenname: P. Mickey surname: Williams fullname: Williams, P. Mickey organization: Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080 – sequence: 12 givenname: Zora surname: Modrusan fullname: Modrusan, Zora organization: Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080 – sequence: 13 givenname: Burt G. surname: Feuerstein fullname: Feuerstein, Burt G. organization: Brain Tumor Research Center, University of California, San Francisco, San Francisco, California 94143 – sequence: 14 givenname: Ken surname: Aldape fullname: Aldape, Ken organization: Department of Pathology, M.D. Anderson Cancer Center, Houston, Texas 77030
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/16530701$$D View this record in MEDLINE/PubMed
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64 16530697 - Cancer Cell. 2006 Mar;9(3):147-8
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Snippet	Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class...
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SubjectTerms	Biomarkers, Tumor - analysis Brain - growth & development Brain Neoplasms - classification Brain Neoplasms - genetics Brain Neoplasms - pathology CELLCYCLE Disease Progression Gene Dosage Gene Expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Glioma - classification Glioma - genetics Glioma - pathology Humans In Situ Hybridization Intracellular Signaling Peptides and Proteins Membrane Proteins - biosynthesis Membrane Proteins - genetics Neoplasm Invasiveness - genetics Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Prognosis PTEN Phosphohydrolase - biosynthesis PTEN Phosphohydrolase - genetics
Title	Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis
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