Characterization of somatic mutations in sporadic uveal melanoma and uveal melanoma in patients with germline BAP1 pathogenic variants

Karin A W Wadt*, Katja Harbst, Mette M B Sjøl, Frida Rosengren, Christina Westmose Yde, Kristoffer Staal Rohrberg, Marlene Richter Jensen, Steffen Heegaard, Jens Folke Kiilgaard, Anne-Marie Gerdes, Nicholas Hayward, Göran B Jönsson

*Corresponding author for this work

Abstract

Genetic analyses were conducted on tumor samples from 88 patients with uveal melanoma (UM), 6 of whom carry pathogenic germline variants in BAP1. We assessed the frequency, pattern, and prognostic significance of somatic aberrations, and investigated differences between germline BAP1 variant carriers compared to sporadic cases. The frequency of the main oncogenic driver mutations was not significantly different between these groups. Patients with germline BAP1 variants did not have significantly different overall survival compared to the wildtype or somatic BAP1 mutation groups. Patients with a somatic BAP1 mutation (n = 24) had a significantly worse prognosis compared to wildtype (n = 58). All patients with stage III tumors and a somatic BAP1 mutation (n = 7) developed metastasis, however four of 28 stage I-II tumors without metastasis had somatic BAP1 mutations, with observation time >5 years. The tumor from one germline BAP1 carrier (stage IIIC) with a somatic EIF1AX splice variant, has not developed metastasis within a 22-year observation time.

Original languageEnglish
Article numbere0306386
JournalPLoS One
Volume19
Issue number10
Pages (from-to)e0306386
ISSN1932-6203
DOIs
Publication statusPublished - 2024

Keywords

  • Humans
  • Ubiquitin Thiolesterase/genetics
  • Melanoma/genetics
  • Uveal Neoplasms/genetics
  • Tumor Suppressor Proteins/genetics
  • Germ-Line Mutation
  • Male
  • Female
  • Middle Aged
  • Aged
  • Adult
  • Prognosis
  • Aged, 80 and over

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