title: 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.
authors.affiliation: Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. david.basanta@kclalumni.net
authors.forename: David
authors.initials: D
authors.lastname: Basanta
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Scott
authors.forename: Russ
authors.initials: R
authors.lastname: Rockne
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Swanson
authors.forename: Alexander R A
authors.initials: AR
authors.lastname: Anderson
mesh_terms: D005716:Game Theory; D005909:Glioblastoma / Q000235:genetics* / Q000556:secondary*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human