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dc.contributor.authorWerner, B
dc.date.accessioned2018-07-18T08:22:01Z
dc.date.issued2016-08
dc.identifierhttp://biologydirect.biomedcentral.com/articles/10.1186/s13062-016-0140-7
dc.identifier.citationBiology Direct, 2016, 11
dc.identifier.issn1745-6150
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2087
dc.description.abstractBackground: It has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, where a small number of tissue specific stem cells produces a large number of specialized progeny during multiple differentiation steps. Another well known mechanism is the spatial organization of stem cell populations and it is thought that this organization suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. Results: We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organization of a cancer suppressing tissue architecture and should be taken into account in arguments for the evolution of such tissues. Conclusion: We show that for systems that are composed of few cells reflecting the typical organization of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special tissue structures that can suppress most types of non-neutral mutations simultaneously.
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectSTEM-CELL DYNAMICS BENEFICIAL MUTATIONS PASSENGER MUTATIONS CLONAL INTERFERENCE EVOLUTION POPULATIONS EPISTASIS HEMATOPOIESIS INITIATION HALLMARKS
dc.titleShould tissue structure suppress or amplify selection to minimize cancer risk?
dc.typeJournal Article
dcterms.dateAccepted2016-06-04
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBiology Direct
pubs.notesISI Document Delivery No.: DV7RC Times Cited: 0 Cited Reference Count: 55 Hindersin, Laura Werner, Benjamin Dingli, David Traulsen, Arne 0 BIOMED CENTRAL LTD LONDON BIOL DIRECT
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.volume11
pubs.embargo.termsNot known
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorWerner, Benjaminen


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