The role of IDH1 mutated tumour cells in secondary glioblastomas: An evolutionary game theoretical view

David Basanta, Jacob G. Scott, Russ Rockne, Kristin R. Swanson, Alexander R.A. Anderson

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Recent advances in clinical medicine have elucidated two significantly different subtypes of which carry very different prognoses, both defined by mutations in isocitrate dehydrogenase-1 (IDH-1). The mechanistic consequences of this mutation have not yet been fully clarified, with conflicting opinions existing in the literature; however, IDH-1 mutation may be used as a surrogate marker to distinguish between primary and secondary glioblastoma multiforme (sGBM) from malignant progression of a lower grade glioma. We develop a mathematical model of IDH-1 mutated secondary glioblastoma using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolytic cells. Our model recapitulates glioblastoma behavior well and is able to reproduce two recent experimental findings, as well as make novel predictions concerning the rate of invasive growth as a function of vascularity, and fluctuations in the proportions of phenotypic populations that a glioblastoma will experience under different microenvironmental constraints.

Original languageEnglish (US)
Article number015016
JournalPhysical Biology
Volume8
Issue number1
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology
  • Cell Biology

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