Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
Welsh, S. J.
Gómez, J. M. M.
Gallagher, F. A.
Miller, M. L.
Campbell, P. J.
Wedge, David C
Adams, D. J.
AffiliationExperimental Cancer Genetics, The Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.
MetadataShow full item record
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.
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.
- TERT, BRAF, and NRAS Mutational Heterogeneity between Paired Primary and Metastatic Melanoma Tumors.
- Authors: Chang GA, Wiggins JM, Corless BC, Syeda MM, Tadepalli JS, Blake S, Fleming N, Darvishian F, Pavlick A, Berman R, Shapiro R, Shao Y, Karlin-Neumann G, Spittle C, Osman I, Polsky D
- Issue date: 2020 Aug
- Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition.
- Authors: Turajlic S, Furney SJ, Stamp G, Rana S, Ricken G, Oduko Y, Saturno G, Springer C, Hayes A, Gore M, Larkin J, Marais R
- Issue date: 2014 May
- Mutation landscape in melanoma patients clinical implications of heterogeneity of BRAF mutations.
- Authors: Heinzerling L, Baiter M, Kühnapfel S, Schuler G, Keikavoussi P, Agaimy A, Kiesewetter F, Hartmann A, Schneider-Stock R
- Issue date: 2013 Nov 26
- Molecular and genetic diversity in the metastatic process of melanoma.
- Authors: Harbst K, Lauss M, Cirenajwis H, Winter C, Howlin J, Törngren T, Kvist A, Nodin B, Olsson E, Häkkinen J, Jirström K, Staaf J, Lundgren L, Olsson H, Ingvar C, Gruvberger-Saal SK, Saal LH, Jönsson G
- Issue date: 2014 May
- Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling.
- Authors: Vergara IA, Mintoff CP, Sandhu S, McIntosh L, Young RJ, Wong SQ, Colebatch A, Cameron DL, Kwon JL, Wolfe R, Peng A, Ellul J, Dou X, Fedele C, Boyle S, Arnau GM, Raleigh J, Hatzimihalis A, Szeto P, Mooi J, Widmer DS, Cheng PF, Amann V, Dummer R, Hayward N, Wilmott J, Scolyer RA, Cho RJ, Bowtell D, Thorne H, Alsop K, Cordner S, Woodford N, Leditschke J, O'Brien P, Dawson SJ, McArthur GA, Mann GJ, Levesque MP, Papenfuss AT, Shackleton M
- Issue date: 2021 Mar 4