Molecular profiling of driver events in metastatic uveal melanoma

Joakim Karlsson, Lisa M. Nilsson, Suman Mitra, Samuel Alsén, Ganesh Vilas Shelke, Vasu R. Sah, Elin M.V. Forsberg, Ulrika Stierner, Charlotta All-Eriksson, Berglind Einarsdottir, Henrik Jespersen, Lars Ny, Per Lindnér, Erik Larsson, Roger Olofsson Bagge, Jonas A. Nilsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.

Original languageEnglish
Article number1894
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2020

Bibliographical note

Funding Information:
The results published here are in part based upon data generated by the TCGA Research Network ( We thank Sofia Stenqvist for animal care, Ola Nilsson and Gülay Altiparmak for histology, Carina Karlsson for technical assistance and Therese Bengtsson, Valerio Belgrano and surgeons in the SCANDIUM trial for patient sampling and registrations. Quantitative proteomic analysis was performed by Britt-Marie Olssen and Evelin Berger at the Proteomics Core Facility of Sahlgrenska Academy, University of Gothenburg. The GeneCoreSU and SciLifeLab facilities are acknowledged for sequencing services, partly financed by a National Genomics Initiative grant to J.A.N. Other funding sources included Knut and Alice Wallenberg Foundation, Cancerfonden, Vetenskaps-rådet, Sjöbergstiftelsen, Familjen Erling Perssons stiftelse, Wilhelm & Martina Lundgrens Vetenskapsfond, the Assar Gabrielsson foundation and Västra Götalandsregionen.

Publisher Copyright:
© 2020, The Author(s).


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