Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Research output: Contribution to journalArticlepeer-review

Authors

  • Roy Rabbie
  • Naser Ansari-pour
  • Oliver Cast
  • Doreen Lau
  • Francis Scott
  • Sarah J. Welsh
  • Christine Parkinson
  • 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. Campbell
  • Pippa Corrie
  • David C. Wedge
  • David J. Adams

Colleges, School and Institutes

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.

Details

Original languageEnglish
JournalNature Communications
Volume11
Issue number1
Early online date27 Jul 2020
Publication statusPublished - 27 Aug 2020