Ophthalmology Science (Mar 2024)

8q Gain Has No Additional Predictive Value in SF3B1MUT Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1MUT Uveal Melanoma

  • Josephine Q.N. Nguyen, MD,
  • Wojtek Drabarek, MD, PhD,
  • Jolanda Vaarwater, BS,
  • Serdar Yavuzyigitoglu, MD, PhD,
  • Robert M. Verdijk, MD, PhD,
  • Dion Paridaens, MD, PhD,
  • Nicole C. Naus, MD, PhD,
  • Annelies de Klein, PhD,
  • Erwin Brosens, PhD,
  • Emine Kiliç, MD, PhD,
  • Emine Kilic,
  • Annelies de Klein,
  • Erwin Brosens,
  • Nicole C. Naus,
  • Dion Paridaens,
  • Serdar Yavuzyigitoglu,
  • Wojtek Drabarek,
  • Josephine Q.N. Nguyen,
  • Jolanda Vaarwater,
  • Robert M. Verdijk

Journal volume & issue
Vol. 4, no. 2
p. 100413

Abstract

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Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 (SF3B1)-mutated (SF3B1MUT) tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of SF3B1MUT UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and SF3B1MUT UM. Design: Retrospective cohort study. Subjects: Patients diagnosed with UM who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included. Methods: Fifty-nine patients with SF3B1MUT tumors and 211 patients with BRCA1 associated protein 1 (BAP1)-mutated (BAP1MUT) tumors were included in this study. Copy number status and gene expression were assessed using either a single nucleotide polymorphism array, fluorescence in situ hybridization, and karyotyping, or a combination of these techniques. Disease-free survival was determined and a cut-off of 60 months was used to define early-onset metastatic disease. Main Outcome Measures: Disease-free survival. Results: Forty-eight patients with SF3B1MUT UM (81%) had chromosome 8q gain (3 copies, 78%; 4 copies, 22%). Kaplan–Meier analysis of SF3B1MUT UM did not indicate a difference in survival in patients with or without gain of 8q (P = 0.99). Furthermore, the number of 8q copies was not associated with survival when comparing early (P = 0.97) versus late (P = 0.23) metastases group. In contrast, the presence of 8q gain (86%) was correlated with a decreased survival in BAP1MUT UM (P = 0.013). Conclusions: We did not find a correlation between 8q gain and early-onset metastasis in SF3B1MUT tumors. Gain of 8q has no additional predictive value in SF3B1MUT tumors. In contrast, 8q gain is predictive of a worse prognosis in patients with BAP1MUT tumors. Thus, gain of chromosome 8q has additional predictive value for BAP1MUT tumors, but not for SF3B1MUT tumors. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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