Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Roy Rabbie, Naser Ansari-pour, Oliver Cast, Doreen Lau, Francis Scott, Sarah J. Welsh, Christine Parkinson, Leila Khoja, Luiza Moore, Mark Tullett, Kim Wong, Ingrid Ferreira, Julia M. Martínez Gómez, Mitchell Levesque, Ferdia A. Gallagher, Alejandro Jiménez-sánchez, Laura Riva, Martin L. Miller, Kieren Allinson, Peter J. CampbellPippa Corrie, David C. Wedge, David J. Adams

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
JournalNature Communications
Issue number1
Early online date27 Aug 2020
Publication statusE-pub ahead of print - 27 Aug 2020


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