Graph models of oncogenesis with an application to melanoma

Michael D. Radmacher, Richard Simon, Richard Desper, Raymond Taetle, Alejandro A. Schäffer, Mark A. Nelson

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We describe several analytical techniques for use in developing genetic models of oncogenesis including: methods for the selection of important genetic events, construction of graph models (including distance-based trees, branching trees, contingency trees and directed acyclic graph models) from these events and methods for interpretation of the resulting models. The models can be used to make predictions about: which genetic events tend to occur early, which events tend to occur together and the likely order of events. Unlike simple path models of oncogenesis, our models allow dependencies to exist between specific genetic changes and allow for multiple, divergent paths in tumor progression. A variety of genetic events can be used with the graph models including chromosome breaks, losses or gains of large DNA regions, small mutations and changes in methylation. As an application of the techniques, we use a recently published cytogenetic analysis of 206 melanoma cases [Nelson et al. (2000), Cancer Genet. Cytogenet. 122, 101-109] to derive graph models for chromosome breaks in melanoma. Among our predictions are: (1) breaks in 6q1 and 1q1 are early events, with 6q1 preferentially occurring first and increasing the probability of a break in 1q1 and (2) breaks in the two sets {1p1, 1p2, 9q1} and {1q1, 7p2, 9p2} tend to occur together. This study illustrates that the application of graph models to genetic data from tumor sets provide new information on the interrelationships among genetic changes during tumor progression.

Original languageEnglish (US)
Pages (from-to)535-548
Number of pages14
JournalJournal of Theoretical Biology
Volume212
Issue number4
DOIs
StatePublished - Oct 21 2001

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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    Radmacher, M. D., Simon, R., Desper, R., Taetle, R., Schäffer, A. A., & Nelson, M. A. (2001). Graph models of oncogenesis with an application to melanoma. Journal of Theoretical Biology, 212(4), 535-548. https://doi.org/10.1006/jtbi.2001.2395