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

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.
AuthorsDavid Basanta, Jacob G Scott, Russ Rockne, Kristin R Swanson, Alexander R A Anderson
JournalPhysical biology (Phys Biol) Vol. 8 Issue 1 Pg. 015016 (Feb 2011) ISSN: 1478-3975 [Electronic] England
PMID21301070 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
Topics
  • Game Theory
  • Glioblastoma (genetics, secondary)
  • Humans
  • Isocitrate Dehydrogenase (genetics)
  • Models, Genetic
  • Mutation

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