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

Molecular profiling of driver events in metastatic uveal melanoma

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  • Media type: E-Article
  • Title: Molecular profiling of driver events in metastatic uveal melanoma
  • Contributor: Karlsson, Joakim; Nilsson, Lisa M.; Mitra, Suman; Alsén, Samuel; Shelke, Ganesh Vilas; Sah, Vasu R.; Forsberg, Elin M. V.; Stierner, Ulrika; All-Eriksson, Charlotta; Einarsdottir, Berglind; Jespersen, Henrik; Ny, Lars; Lindnér, Per; Larsson, Erik; Olofsson Bagge, Roger; Nilsson, Jonas A.
  • imprint: Springer Science and Business Media LLC, 2020
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-020-15606-0
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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. <jats:italic>BAP1</jats:italic> alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional <jats:italic>BAP1</jats:italic> 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. <jats:italic>CDKN2A</jats:italic> 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 <jats:italic>TIM-3</jats:italic>, <jats:italic>TIGIT</jats:italic> and <jats:italic>LAG3</jats:italic> 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.</jats:p>
  • Access State: Open Access