Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

Greenman, C. D., Cooke, S.L. , Marshall, J., Stratton, M. R. and Campbell, P. J. (2016) Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process. Journal of Mathematical Biology, 72(1-2), pp. 47-86. (doi: 10.1007/s00285-015-0875-2) (PMID:25833184) (PMCID:PMC4702116)

Abstract

Breakage–fusion–bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then ‘unfolds’ into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. Here we study the evolution space of breakage–fusion–bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2n(n−1)22n(n−1)2 qualitatively distinct evolutions involving nn breakage–fusion–bridge cycles. Secondly we consider the stochastic nature of the process to show these evolutions are not equally likely, and also describe how amplicons become localized. Finally we highlight these methods by inferring the evolution of breakage–fusion–bridge cycles with data from primary tissue cancer samples.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooke, Dr Susie
• Authors: Greenman, C. D., Cooke, S.L., Marshall, J., Stratton, M. R., and Campbell, P. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Mathematical Biology
• Publisher: Springer
• ISSN: 0303-6812
• ISSN (Online): 1432-1416
• Published Online: 02 April 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published inJournal of Mathematical Biology 72(1-2):47-86
• Publisher Policy: Reproduced under a Creative Commons License