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Original Investigation
January 2, 2020

Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival

Author Affiliations
  • 1Unit 830 (Cancer, Heterogeneity, Instability and Plasticity) INSERM, Institut Curie, PSL Research University, Paris, France
  • 2Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France
  • 3Department of Genetics, Institut Curie, PSL Research University, Paris, France
  • 4Department of Biometry, Institut Curie, PSL Research University, Paris, France
  • 5Department of Biopathology, Institut Curie, PSL Research University, Paris, France
  • 6Faculty of Medicine, University of Paris Descartes, Paris, France
  • 7Department of Medical Imaging, Institut Curie, PSL Research University, Paris, France
  • 8Department of Surgical Oncology, Institut Curie, PSL Research University, Paris, France
  • 9Department of Translational Research, Institut Curie, PSL Research University, Paris, France
  • 10Department of Ocular Oncology, Institut Curie, PSL Research University, Paris, France
JAMA Ophthalmol. Published online January 2, 2020. doi:10.1001/jamaophthalmol.2019.5403
Key Points

Question  What is the association of partial chromosome 3 deletion in uveal melanomas with metastasis-free survival?

Findings  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.

Meaning  These findings suggest that uveal melanomas that carry a partial deletion of chromosome 3 encompassing the BAP1 locus have a poor prognosis.

Abstract

Importance  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.

Objective  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.

Exposure  Uveal melanoma with or without partial loss of chromosome 3.

Main Outcomes and Measures  Metastasis-free survival and overall survival at 60 months.

Results  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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