title: Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process.
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 [Formula: see text] qualitatively distinct evolutions involving [Formula: see text] 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.
authors.affiliation: School of Computing Sciences, University of East Anglia, Norwich, UK. C.Greenman@uea.ac.uk.|The Genome Analysis Centre, Norwich Research Park, Norwich, UK. C.Greenman@uea.ac.uk.
authors.forename: C D
authors.initials: CD
authors.lastname: Greenman
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Cooke
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: J
authors.initials: J
authors.lastname: Marshall
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Department of Haematology, University of Cambridge, Cambridge, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Campbell
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D053960:DNA Breaks; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D055641:Mathematical Concepts; D008957:Models, Genetic; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009690:Nucleic Acid Conformation; D013269:Stochastic Processes
chemical_list: D004273:DNA, Neoplasm
keywords: 05A05; 60G99; 92B05; 92D15; 92D20
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