Identification of p18INK4c as a tumor suppressor gene in glioblastoma multiforme

Academic Article

Abstract

  • 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 p16 and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. Here,we describe deletion of the p18 cdk inhibitor as a novel genetic alteration driving the pathogenesis of GBM. Deletions of p18 often occurred in tumors also harboring homozygous deletions of p16 . Expression of p was completely absent in 43% of GBM primary tumors studied by immunohistochemistry. Lentiviral reconstitution of p18 expression at physiologic levels in p18 -deficient but not p18 -proficient GBM cells led to senescence-like G cell cycle arrest. These studies identify p18 as a GBM tumor suppressor gene,revealing an additional mechanism leading to aberrant activation of cyclin/cdk complexes in this terrible malignancy. ©2008 American Association for Cancer Research. INK4a INK4c INK4c INK4a 18INK4c INK4c INK4c INK4c INK4c 1
  • Authors

    Published In

  • Cancer Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Solomon DA; Kim JS; Jenkins S; Ressom H; Huang M; Coppa N; Mabanta L; Bigner D; Yan H; Jean W
  • Start Page

  • 2564
  • End Page

  • 2569
  • Volume

  • 68
  • Issue

  • 8