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

Phys Biol. 2011 Feb;8(1):015016. doi: 10.1088/1478-3975/8/1/015016. Epub 2011 Feb 7.

Abstract

Recent advances in clinical medicine have elucidated two significantly different subtypes of glioblastoma 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Game Theory
  • Glioblastoma / genetics*
  • Glioblastoma / secondary*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Models, Genetic
  • Mutation*

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human