AKT pathway genes define 5 prognostic subgroups in glioblastoma

Anna Joy, Archana Ramesh, Ivan Smirnov, Mark Reiser, Anjan Misra, William R. Shapiro, Gordon B. Mills, Seungchan Kim, Burt G. Feuerstein

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Activity of GFR/PI3K/AKT pathway inhibitors in glioblastoma clinical trials has not been robust. We hypothesized variations in the pathway between tumors contribute to poor response. We clustered GBM based on AKT pathway genes and discovered new subtypes then characterized their clinical and molecular features. There are at least 5 GBM AKT subtypes having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components. Gene Ontology terms indicate a different cell of origin or dominant phenotype for each subgroup. Evidence suggests one subtype is very sensitive to BCNU or CCNU (median survival 5.8 vs. 1.5 years; BCNU/CCNU vs other treatments; respectively). AKT subtyping advances previous approaches by revealing additional subgroups with unique clinical and molecular features. Evidence indicates it is a predictive marker for response to BCNU or CCNU and PI3K/AKT/mTOR pathway inhibitors. We anticipate Akt subtyping may help stratify patients for clinical trials and augment discovery of class-specific therapeutic targets.

Original languageEnglish (US)
Article numbere100827
JournalPloS one
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Joy, A., Ramesh, A., Smirnov, I., Reiser, M., Misra, A., Shapiro, W. R., Mills, G. B., Kim, S., & Feuerstein, B. G. (2014). AKT pathway genes define 5 prognostic subgroups in glioblastoma. PloS one, 9(7), [e100827]. https://doi.org/10.1371/journal.pone.0100827