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dc.contributor.authorRabbie, R.
dc.contributor.authorAnsari-Pour, N.
dc.contributor.authorCast, O.
dc.contributor.authorLau, D.
dc.contributor.authorScott, F.
dc.contributor.authorWelsh, S. J.
dc.contributor.authorParkinson, C.
dc.contributor.authorKhoja, L.
dc.contributor.authorMoore, L.
dc.contributor.authorTullett, M.
dc.contributor.authorWong, K.
dc.contributor.authorFerreira, I.
dc.contributor.authorGómez, J. M. M.
dc.contributor.authorLevesque, M.
dc.contributor.authorGallagher, F. A.
dc.contributor.authorJiménez-Sánchez, A.
dc.contributor.authorRiva, L.
dc.contributor.authorMiller, M. L.
dc.contributor.authorAllinson, K.
dc.contributor.authorCampbell, P. J.
dc.contributor.authorCorrie, P.
dc.contributor.authorWedge, David C
dc.contributor.authorAdams, D. J.
dc.date.accessioned2020-10-06T13:33:49Z
dc.date.available2020-10-06T13:33:49Z
dc.date.issued2020en
dc.identifier.citationRabbie R, Ansari-Pour N, Cast O, Lau D, Scott F, Welsh SJ, et al. Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases. Nat Commun. 2020;11(1):4306.en
dc.identifier.pmid32855398en
dc.identifier.doi10.1038/s41467-020-18060-0en
dc.identifier.urihttp://hdl.handle.net/10541/623344
dc.description.abstractMetastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41467-020-18060-0en
dc.titleMulti-site clonality analysis uncovers pervasive heterogeneity across melanoma metastasesen
dc.typeArticleen
dc.contributor.departmentExperimental Cancer Genetics, The Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.en
dc.identifier.journalNature Communicationsen
dc.description.noteen]
refterms.dateFOA2020-10-07T13:29:56Z


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