title: Rapid and convergent evolution in the glioblastoma multiforme genome.
abstract: Determining which mutations drive tumor progression is a defining question in cancer genomics. We analyzed sequence evolution in Glioblastoma multiforme (GBM) by computing the number of parallel mutations and by estimating ω=dN/dS, a measure of the strength and direction of selection. The ω values of almost all 7617 mutated genes in GBM are much higher than in germline genes. We identified only 21 genes under significant positive selection in GBM, as well as 29 genes under significant purifying selection, including several zinc finger proteins. Therefore, most of the high ω values in the GBM genome are due to weaker purifying selection rather than positive selection. We also found multiple recurrent mutations in GBM, several of which are associated with patient survival time. Our results suggest that convergence and neutral evolution play a significant role in GBM, and that sites with recurrent mutations can serve as molecular diagnostics of the clinical course of GBM tumors.
authors.affiliation: NeuroTexas Institute, St. David's Healthcare, Austin, TX 78705, United States; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, United States; Fresh Pond Research Institute, Cambridge, MA 02140, United States. Electronic address: shpak.max@gmail.com.
authors.forename: Max
authors.initials: M
authors.lastname: Shpak
authors.affiliation: Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Goldberg
authors.affiliation: NeuroTexas Institute, St. David's Healthcare, Austin, TX 78705, United States; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, United States; Texas Advanced Computing Center, University of Texas at Austin, Austin, TX 78758, United States.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cowperthwaite
mesh_terms: D019143:Evolution, Molecular; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D009154:Mutation
keywords: Convergent evolution; Glioblastoma multiforme; Missense mutation; Neutral evolution; Somatic evolution