Journal article
Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 2.8MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-020-18060-0
Authors
- Publisher:
- Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 4306
- Publication date:
- 2020-08-27
- Acceptance date:
- 2020-07-27
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Pmid:
-
32855398
- Language:
-
English
- Keywords:
- Pubs id:
-
1129432
- Local pid:
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pubs:1129432
- Deposit date:
-
2021-03-04
Terms of use
- Copyright holder:
- Rabbie et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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