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 journalArticlepeer-review

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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