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 and Jonas A. Nilsson ()
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Joakim Karlsson: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Lisa M. Nilsson: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Suman Mitra: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Samuel Alsén: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Ganesh Vilas Shelke: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Vasu R. Sah: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Elin M. V. Forsberg: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Ulrika Stierner: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Charlotta All-Eriksson: St. Erik Eye Hospital
Berglind Einarsdottir: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Henrik Jespersen: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Lars Ny: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Per Lindnér: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Erik Larsson: University of Gothenburg
Roger Olofsson Bagge: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital
Jonas A. Nilsson: Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15606-0

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