Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas

Neuropathol Appl Neurobiol. 2005 Oct;31(5):486-90. doi: 10.1111/j.1365-2990.2005.00660.x.


Glioblastomas frequently carry genetic alterations resulting in an aberrant activation of the phosphoinositol-3-kinase (Pi3k)/protein kinase B (Akt) signalling pathway, including most notably phosphatase and tensin homolog (PTEN) mutation, epidermal growth factor receptor (EGFR) amplification and rearrangement, as well as carboxyl-terminal modulator protein (CTMP) hypermethylation [Knobbe et al., (2004) Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas. J Natl Cancer Institute, 96, 483-486]. Here, we investigated two further Pi3k/Akt pathway genes, namely PIK3CA (3q26.3) and phosphatidylinositol-3-kinase enhancer (PIKE) (CENTG1, 12q14), for genetic alteration and aberrant expression in a series of 97 primary glioblastomas. Single strand conformation polymorphism (SSCP) analysis of PIK3CA revealed somatic mutations in five tumours (5%). Twelve glioblastomas (12%) showed amplification of PIKE with invariable co-amplification of the adjacent CDK4 gene. All tumours with PIKE amplification as well as the vast majority of glioblastomas without amplification demonstrated increased expression of PIKE-A but not PIKE-S/L transcripts as compared with non-neoplastic brain tissue. Taken together, our data support an important role of PIK3CA and PIKE gene aberrations in the molecular pathogenesis of primary glioblastomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Child
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics*
  • Female
  • GTP-Binding Proteins / biosynthesis
  • GTP-Binding Proteins / genetics*
  • GTPase-Activating Proteins / biosynthesis
  • GTPase-Activating Proteins / genetics*
  • Gene Amplification
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / biosynthesis
  • Phosphatidylinositol 3-Kinases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA, Neoplasm
  • GTPase-Activating Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AGAP2 protein, human
  • GTP-Binding Proteins