title: Stress-induced DNA damage: a case study in diffuse large B-cell lymphoma.
abstract: DNA damage is one of the mechanisms of mutagenesis. Sequence integrity may be affected by the action of thermal changes, chemical agents, both endogenous and exogenous, and other environmental issues. Abnormally high mutation rates are referred to as genomic instability: a phenomenon closely related to the onset of cancer. Mutant genotypes may be able to confer some kind of selective advantage on subclonal cell populations, leading them to multiply until dominance in a localized tissue environment that later becomes the tumour. Cellular stress, especially that of oxidative and ionic nature, is a recognized trigger for DNA-damaging processes. A physico-chemical model has shown that high hysteresis rates in DNA denaturation curves may be indicative of dissipative processes inducing DNA damage, thus potentially leading to uncontrolled mutagenesis and genome instability. We here study selectively to what extent this phenomenon may occur by analysing the sequence length and composition effects on the thermodynamic behaviour and the presence of hysteresis in pressure-driven DNA denaturation; pronounced hysteresis in the denaturation/renaturation curves may indicate thermal susceptibility to DNA damage. In particular, we consider highly mutated regions of the genome characterized in diffuse large B-cell lymphoma on a recent whole exome next-generation sequencing effort.
authors.affiliation: Division of Sciences and Engineering, University of Guanajuato, León, Mexico.
authors.forename: Luz Adriana
authors.initials: LA
authors.lastname: Nicasio-Collazo
authors.affiliation: Division of Sciences and Engineering, University of Guanajuato, León, Mexico.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Delgado-González
authors.affiliation: Division of Sciences and Engineering, University of Guanajuato, León, Mexico ramoncp@fisica.ugto.mx.
authors.forename: Ramón
authors.initials: R
authors.lastname: Castañeda-Priego
authors.affiliation: Department of Computational Genomics, National Institute of Genomic Medicine, Mexico City, Mexico Complexity in Systems Biology, Center for Complexity Sciences, National Autonomous University of México, Mexico City, Mexico ehernandez@inmegen.gob.mx.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Lemus
mesh_terms: D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D013312:Stress, Physiological
chemical_list: D004273:DNA, Neoplasm
keywords: B-cell lymphoma; DNA denaturation; non-equilibrium thermodynamics