Modeling the dynamics of chromosomal alteration progression in cervical cancer: A computational model

PLoS One. 2017 Jul 19;12(7):e0180882. doi: 10.1371/journal.pone.0180882. eCollection 2017.

Abstract

Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression. The analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose them to cancer progression. The study of somatic alterations through computer simulations of cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Non-deleterious chromosomal alterations contribute to this progression.

MeSH terms

  • Cervix Uteri / pathology*
  • Chromosome Aberrations*
  • Computer Simulation*
  • Disease Progression
  • Female
  • Humans
  • Models, Theoretical*
  • Mutation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Grants and funding

This work was partially supported by PRODEP-SEP, Mexico and our wages. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.