Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in absolute number of 8q-copies correlated with an even shorter survival. SF3B1-mutated (SF3B1MUT) tumors display structural chromosomal anomalies and frequently show 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.
Retrospective cohort study.
Patients diagnosed with UM and who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included.
Fifty-nine patients with SF3B1MUT tumors and 211 patients with BAP1MUT tumors were included in this study. Copy number status and gene expression were assessed using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH) and/or karyotyping. Disease-free survival (DFS) was determined and a cut-off of 60 months was used to define early-onset metastatic disease.
Main outcome measures
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) vs late (p=0.23) metastases group. In contrast, presence of 8q gain (86%) was correlated with a decreased survival in BAP1MUT UM (p=0.013).
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 for 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.
|Publication status||E-pub ahead of print - 16 Oct 2023|