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Cancer Research 68, 2564-2569, April 15, 2008. Published Online First April 1, 2008;
doi: 10.1158/0008-5472.CAN-07-6388
© 2008 American Association for Cancer Research

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Priority Reports

Identification of p18INK4c as a Tumor Suppressor Gene in Glioblastoma Multiforme

David A. Solomon1, Jung-Sik Kim1, Sultan Jenkins1, Habtom Ressom1, Michael Huang2, Nicholas Coppa2, Lauren Mabanta1, Darell Bigner3, Hai Yan3, Walter Jean2 and Todd Waldman1

1 Lombardi Comprehensive Cancer Center, 2 Department of Neurosurgery, Georgetown University School of Medicine, Washington, District of Columbia, and 3 Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Requests for reprints: Todd Waldman, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, NRB E304, 3970 Reservoir Road, Northwest, Washington, DC 20057. Phone: 202-687-1340; Fax: 202-687-7505; E-mail: waldmant{at}georgetown.edu.

Key Words: tumor suppressor gene • glioblastoma multiforme • p18INK4c • cdk inhibitor • homozygous deletion

Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygous deletion of p16INK4a and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. Here, we describe deletion of the p18INK4c cdk inhibitor as a novel genetic alteration driving the pathogenesis of GBM. Deletions of p18INK4c often occurred in tumors also harboring homozygous deletions of p16INK4a. Expression of p18INK4c was completely absent in 43% of GBM primary tumors studied by immunohistochemistry. Lentiviral reconstitution of p18INK4c expression at physiologic levels in p18INK4c-deficient but not p18INK4c-proficient GBM cells led to senescence-like G1 cell cycle arrest. These studies identify p18INK4c as a GBM tumor suppressor gene, revealing an additional mechanism leading to aberrant activation of cyclin/cdk complexes in this terrible malignancy. [Cancer Res 2008;68(8):2564–9]







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.