What is the association of partial chromosome 3 deletion in uveal melanomas with metastasis-free survival?
In this cohort study, partial deletions of chromosome 3 encompassing the BAP1 locus were associated with lower metastasis-free survival at 60 months compared with uveal melanomas without such deletion.
These findings suggest that uveal melanomas that carry a partial deletion of chromosome 3 encompassing the BAP1 locus have a poor prognosis.
Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined.
To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival.
Design, Setting, and Participants
This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017.
Uveal melanoma with or without partial loss of chromosome 3.
Main Outcomes and Measures
Metastasis-free survival and overall survival at 60 months.
Of the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001).
Conclusions and Relevance
These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.
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Rodrigues M, Ait Rais K, Salviat F, et al. Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival. JAMA Ophthalmol. Published online January 02, 2020. doi:10.1001/jamaophthalmol.2019.5403
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