Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

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&#39;Brien, P; Dawson, SJ; McArthur, GA; Mann, GJ; Levesque, MP; Papenfuss, AT; Shackleton, M

Author(s): 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;
Details: Publication Year 2021-03-04,Volume 12,Issue #1,Page 1434
Journal Title: Nature Communications
Abstract: Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.
Publisher: NPG
Research Division(s): Bioinformatics
PubMed ID: 33664264
Publisher's Version: https://doi.org/10.1038/s41467-021-21576-8
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-021-21576-8
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Vergara IA et al_Nature Comms_2021.pdf - (2.84MB, application/pdf)

Creation Date: 2021-05-13 09:20:24

Last Modified: 2021-05-13 11:16:26