Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
Authors
Rabbie, R.Ansari-Pour, N.
Cast, O.
Lau, D.
Scott, F.
Welsh, S. J.
Parkinson, C.
Khoja, L.
Moore, L.
Tullett, M.
Wong, K.
Ferreira, I.
Gómez, J. M. M.
Levesque, M.
Gallagher, F. A.
Jiménez-Sánchez, A.
Riva, L.
Miller, M. L.
Allinson, K.
Campbell, P. J.
Corrie, P.
Wedge, David C
Adams, D. J.
Affiliation
Experimental Cancer Genetics, The Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.Issue Date
2020
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Show full item recordAbstract
Metastatic 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.Citation
Rabbie 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.Journal
Nature CommunicationsDOI
10.1038/s41467-020-18060-0PubMed ID
32855398Additional Links
https://dx.doi.org/10.1038/s41467-020-18060-0Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-18060-0
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