Fig. 2.

Cultures with PIK3CA mutations, or constitutively high Akt phosphorylation, show significantly reduced sensitivity to NVP-AEW541. (A) PIK3CA mutations in glioblastoma cultures. Chromatograms show sequences derived from exon sequencing of genomic DNA. The chromatograms show the results from the sequencing of 5 cultures with wild-type PIK3CA and 2 cultures with activating E542K mutation. Positions of mutations in cultures 21 and 34 are indicated by an arrow, and the amino acid alterations are indicated above the chromatograms. (B) Basal and IGF-1-induced changes in Akt phosphorylation. The experiment was performed 4 times for each culture and yielded similar results. (C) Growth inhibition in different subsets of glioblastoma cultures. Results from Fig. 1A were used to compare the average growth inhibition in cultures without detected alteration in PI3K/PTEN/Akt, with activating mutations in PIK3CA and with ligand-independent Akt phosphorylation (Student's t-test).