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Modeling the Evolution of Ploidy in a Resource Restricted Environment

  • Gregory Kimmel
  • Jill Barnholtz-Sloan
  • Hanlee Ji
  • Philipp Altrock
  • Noemi AndorEmail author
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 11826)

Abstract

Gliomas are tumors that evolve from glial cells in the brain or spine. Most gliomas are diagnosed as either lower-grade lesions (grade II) or Glioblastoma (grade IV). Progression of lower-grade gliomas (LGG) to Glioblastoma (GBM) is accompanied by a phenotypic switch to a highly invasive tumor cell phenotype. Converging evidence from different cancer types, including colorectal-, breast-, and lung- cancers, suggests a strong enrichment of high ploidy cells among metastatic lesions as compared to the primary tumor [1, 2]. Even in normal development: trophoblast giant cells - the first cell type to terminally differentiate during embryogenesis - are responsible for invading the placenta and strikingly these cells can have up to 1000 copies of the genome [5]. All this points to the existence of a ubiquitous mechanism that links high DNA content to an invasive phenotype. We formulate a mechanistic Grow-or-go model that postulates higher energy demands of high-ploidy cells as a driver of their invasive behavior. We will test whether this mechanism may contribute to the quick recurrence of GBMs after surgery [7] and whether it can explain striking differences in the prognostic power of integrin signaling and cell cycle progression between males and females [13].

Keywords

Ploidy Glioblastoma Mathematical modeling 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gregory Kimmel
    • 1
  • Jill Barnholtz-Sloan
    • 3
  • Hanlee Ji
    • 2
  • Philipp Altrock
    • 1
  • Noemi Andor
    • 1
    Email author
  1. 1.Integrated Mathematical OncologyMoffitt Cancer CenterTampaUSA
  2. 2.School of MedicineStanford UniversityStanfordUSA
  3. 3.Case Comprehensive Cancer Center, Cleveland Institute for Computational BiologyCase Western Reserve University School of MedicineClevelandUSA

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