Mutations of PTEN and the PI3K-AKT pathway in T-ALL. (A) Sequencing of PTEN in 44 of the primary samples shown in Figure 1 identified nonsynonymous sequence alterations in 12 of these samples, all of which were predicted to disrupt the PTEN protein within an 18-amino acid region of the C2 domain. Note that the specific mutations in cases 14 and 27 were impossible to determine because of the presence of 2 simultaneous frameshift sequences. (B) Targeted sequencing of PIK3R1, PIK3CA, and AKT1-3 exons known to be mutated in human cancer identified nonsynonymous sequence alterations in PTEN and the PI3K-AKT pathway in 47.7% of primary T-ALL cases. Lesions within the PTEN-PI3K-AKT pathway were mutually exclusive. Abnormalities in the NF1 and RAS genes were also identified but were not solely associated with PTEN-PI3K-AKT pathway abnormalities. *Novel in-frame insertion/deletions. (C-D) Kaplan-Meier event-free survival curves for the 44 cases analyzed by CGH and sequencing demonstrate that, overall, genetic alterations of the PTEN-PI3K-AKT pathway did not predict event-free survival, whereas deletions of PTEN were significantly associated with early treatment failure.