Graph models of oncogenesis with an application to melanoma

Citation
Md. Radmacher et al., Graph models of oncogenesis with an application to melanoma, J THEOR BIO, 212(4), 2001, pp. 535-548
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
JOURNAL OF THEORETICAL BIOLOGY
ISSN journal
0022-5193 → ACNP
Volume
212
Issue
4
Year of publication
2001
Pages
535 - 548
Database
ISI
SICI code
0022-5193(20011021)212:4<535:GMOOWA>2.0.ZU;2-5
Abstract
We describe several analytical techniques for use in developing genetic mod els of oncogenesis including: methods for the selection of important geneti c events, construction of graph models (including distance-based trees, bra nching trees, contingency trees and directed acyclic graph models) from the se events and methods for interpretation of the resulting models. The model s 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 p aths in tumor progression. A variety of genetic events can be used with the graph models including chromosome breaks, losses or gains of large DNA reg ions, small mutations and changes in methylation. As an application of the techniques, we use a recently published cytogenetic analysis of 206 melanom a cases [Nelson et al. (2000), Cancer Genet. Cytogenet. 122, 101-109] to de rive graph models for chromosome breaks in melanoma. Among our predictions are: (1) breaks in 6q1 and 1q1 are early events, with 6q1 preferentially oc curring first and increasing the probability of a break in 1q1 and (2) brea ks in the two sets {1p1, 1p2, 9q1}, and {1q1, 7p2, 9p2} tend to occur toget her. This study illustrates that the application of graph models to genetic data from tumor sets provide new information on the interrelationships amo ng genetic changes during tumor progression. (C), 2001 Academic Press.