AKT pathway genes define 5 prognostic subgroups in glioblastoma

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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
Externally publishedYes

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Lomustine
Carmustine
phosphatidylinositol 3-kinase
Glioblastoma
Phosphatidylinositol 3-Kinases
Genes
Tumors
clinical trials
Clinical Trials
Gene Ontology
tumor suppressor genes
genes
oncogenes
Tumor Suppressor Genes
Oncogenes
Ontology
Phenotype
Gene Expression
phenotype
therapeutics

ASJC Scopus subject areas

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

Cite this

Joy, A., Ramesh, A., Smirnov, I., Reiser, M., Misra, A., Shapiro, W. R., ... 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

AKT pathway genes define 5 prognostic subgroups in glioblastoma. / Joy, Anna; Ramesh, Archana; Smirnov, Ivan; Reiser, Mark; Misra, Anjan; Shapiro, William R.; Mills, Gordon; Kim, Seungchan; Feuerstein, Burt G.

In: PLoS One, Vol. 9, No. 7, e100827, 01.07.2014.

Research output: Contribution to journalArticle

Joy, A, Ramesh, A, Smirnov, I, Reiser, M, Misra, A, Shapiro, WR, Mills, G, Kim, S & Feuerstein, BG 2014, 'AKT pathway genes define 5 prognostic subgroups in glioblastoma', PLoS One, vol. 9, no. 7, e100827. https://doi.org/10.1371/journal.pone.0100827
Joy A, Ramesh A, Smirnov I, Reiser M, Misra A, Shapiro WR et al. AKT pathway genes define 5 prognostic subgroups in glioblastoma. PLoS One. 2014 Jul 1;9(7). e100827. https://doi.org/10.1371/journal.pone.0100827
Joy, Anna ; Ramesh, Archana ; Smirnov, Ivan ; Reiser, Mark ; Misra, Anjan ; Shapiro, William R. ; Mills, Gordon ; Kim, Seungchan ; Feuerstein, Burt G. / AKT pathway genes define 5 prognostic subgroups in glioblastoma. In: PLoS One. 2014 ; Vol. 9, No. 7.
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