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

Abstract

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.

• Authors: C B Knobbe, A Trampe-Kieslich, G Reifenberger
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 31 Issue 5 Pg. 486-90 (Oct 2005) ISSN: 0305-1846 [Print] England
• PMID: 16150119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, genetics)
• GTPase-Activating Proteins (biosynthesis, genetics)
• Gene Amplification
• Glioblastoma (genetics)
• Humans
• Male
• Middle Aged
• Phosphatidylinositol 3-Kinases (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction