dc.contributor.author | Opasic, L | en_US |
dc.contributor.author | Zhou, D | en_US |
dc.contributor.author | Werner, B | en_US |
dc.contributor.author | Dingli, D | en_US |
dc.contributor.author | Traulsen, A | en_US |
dc.date.accessioned | 2020-03-02T15:21:46Z | |
dc.date.available | 2019-04-11 | en_US |
dc.date.issued | 2019-04-29 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/62989 | |
dc.description.abstract | BACKGROUND: Modern cancer treatment strategies aim to target tumour specific genetic (or epigenetic) alterations. Treatment response improves if these alterations are clonal, i.e. present in all cancer cells within tumours. However, the identification of truly clonal alterations is impaired by the tremendous intra-tumour genetic heterogeneity and unavoidable sampling biases. METHODS: Here, we investigate the underlying causes of these spatial sampling biases and how the distribution and sizes of biopsies in sampling protocols can be optimised to minimize such biases. RESULTS: We find that in the ideal case, less than a handful of samples can be enough to infer truly clonal mutations. The frequency of the largest sub-clone at diagnosis is the main factor determining the accuracy of truncal mutation estimation in structured tumours. If the first sub-clone is dominating the tumour, higher spatial dispersion of samples and larger sample size can increase the accuracy of the estimation. In such an improved sampling scheme, fewer samples will enable the detection of truly clonal alterations with the same probability. CONCLUSIONS: Taking spatial tumour structure into account will decrease the probability to misclassify a sub-clonal mutation as clonal and promises better informed treatment decisions. | en_US |
dc.format.extent | 403 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | BMC Cancer | en_US |
dc.rights | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | |
dc.subject | Clonal mutations | en_US |
dc.subject | Intratumour heterogeneity | en_US |
dc.subject | Somatic evolution | en_US |
dc.subject | Spatial model | en_US |
dc.subject | Targeted therapy | en_US |
dc.subject | Truncal mutations | en_US |
dc.subject | Algorithms | en_US |
dc.subject | Cell Count | en_US |
dc.subject | Clone Cells | en_US |
dc.subject | Genetic Heterogeneity | en_US |
dc.subject | Humans | en_US |
dc.subject | Models, Theoretical | en_US |
dc.subject | Mutation | en_US |
dc.subject | Neoplasms | en_US |
dc.title | How many samples are needed to infer truly clonal mutations from heterogenous tumours? | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s). 2019 | |
dc.identifier.doi | 10.1186/s12885-019-5597-1 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31035962 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 19 | en_US |
dcterms.dateAccepted | 2019-04-11 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |