Abstract 3688: Akt pathway genes classify GBM into 6 prognostic subgroups with different clinical and molecular features

Abstract

Abstract The Akt pathway is a therapeutic target in Glioblastoma Multiforme (GBM) and an important determinant of patient outcome. However, it is not known if akt pathway variations exist in GBM tumors. To investigate we developed a list of Akt pathway genes and investigated expression subgroups in a set of human GBM. Akt classification divides GBM into 6 subgroups with differing survivals and clinical/molecular features. Median survival of patients in the longest surviving subgroup (subgroup 5) was 3.9 yr vs 0.75 yr for patients in the shortest surviving subgroup (p < 0.01 Bonferroni corrected log rank). Patients in the long surviving subgroup were younger than the rest (median age = 38 vs 49 respectively; p = 0.05 corrected for multiple comparisons), but survival differences were independent of age (p = 0.027; subgroup 5 vs the rest). Tumors in short surviving subgroups were characterized by chr7 gain, chr10 loss and high ser473 phosphorylated-akt (p-akt) staining. The long surviving subgroup tumors were enriched for chr19q loss, low p-akt staining, elevated Notch staining and had no DNA copy number alterations in chr7 or chr10. Previously described subgroups (Phillips et.al.) were enriched in akt subgroups (all with p<0.001). These results suggest that tumors with a pathological diagnosis of GBM are a collection of molecular subgroups with fundamental differences in biology and clinical behavior. We hypothesize that Akt subgroups will enhance drug discovery and help personalize treatment for GBM therapeutics. Supported by Barrow Neurological Foundation (BGF and AMJ), Halle Family Foundation (BGF), and NIH 1 K01 NS064952-01A1 (AMJ). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3688. doi:1538-7445.AM2012-3688