Glioblastomas frequently carry mutations in the PTEN tumor suppressor gene on 10q23.3. The
tumor suppressor properties of Pten are closely related to its inhibitory effect on the phosphatidyl-inositol-3'-kinase (Pi3k)-dependent activation of
protein kinase B (Akt) signalling. Here, we report on the analysis of 17 genes related to the Pi3k/Akt signalling pathway for genetic alteration and aberrant expression in a series of 103
glioblastomas. Mutation, homozygous deletion or loss of expression of PTEN was detected in 32% of the
tumors. In contrast, we did not find any aberrations in the
inositol polyphosphate phosphatase like-1 gene (INPPL1), whose gene product may also counteract Pi3k-dependent Akt activation. Analysis of genes encoding
proteins that may activate the pathway upstream of Pi3k revealed variable fractions of
tumors with EGFR amplification (31%), PDGFRA amplification (8%), and IRS2 amplification (2%). The
protein tyrosine kinase 2 (PTK2/FAK1) gene was neither amplified nor overexpressed at the
mRNA level. Investigation of three genes encoding catalytic subunits of Pi3k (PIK3CA, PIK3CD, and PIK3C2B) revealed amplification of PIK3C2B (1q32) in 6
tumors (6%). Overexpression of PIK3C2B
mRNA was detected in 4 of these cases. PIK3CD (1p36.2) and PIK3CA (3q26.3) were not amplified but PIK3CD
mRNA was overexpressed in 6
tumors (6%). Amplification and overexpression of AKT1 was detected in a single case of
gliosarcoma. The IRS1, PIK3R1, PIK3R2, AKT2, AKT3, FRAP1, and RPS6KB1 genes were neither amplified nor overexpressed in any of the
tumors. Taken together, our data indicate that different genes related to the Pi3k/Akt signalling pathway may be aberrant in
glioblastomas.