Glioblastoma: Defining Tumor Niches
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TL;DR: The features and functions of the distinct GBM niches are reviewed, the different cell constituents and the functional status of the vasculature are detailed, and prospects of therapeutically targeting GBM niche constituents are discussed.
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Abstract: Glioblastomas (GBM) are one of the most recalcitrant brain tumors because of their aggressive invasive growth and resistance to therapy. They are highly heterogeneous malignancies at both the molecular and histological levels. Specific histological hallmarks including pseudopalisading necrosis and microvascular proliferation distinguish GBM from lower-grade gliomas, and make GBM one of the most hypoxic as well as angiogenic tumors. These microanatomical compartments present specific niches within the tumor microenvironment that regulate metabolic needs, immune surveillance, survival, invasion as well as cancer stem cell maintenance. Here we review features and functions of the distinct GBM niches, detail the different cell constituents and the functional status of the vasculature, and discuss prospects of therapeutically targeting GBM niche constituents.
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
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TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
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