Manuel Rodrigues1,2, Khadija Ait Rais3, Flore Salviat4, Nathalie Algret4, Fatoumata Simaga3, Raymond Barnhill5,6, Sophie Gardrat1,5, Vincent Servois7, Pascale Mariani8, Sophie Piperno-Neumann2, Sergio Roman-Roman9, Olivier Delattre1,3, Nathalie Cassoux6,10, Alexia Savignoni4, Marc-Henri Stern1,3, Gaëlle Pierron3. 1. Unit 830 (Cancer, Heterogeneity, Instability and Plasticity) INSERM, Institut Curie, PSL Research University, Paris, France. 2. Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France. 3. Department of Genetics, Institut Curie, PSL Research University, Paris, France. 4. Department of Biometry, Institut Curie, PSL Research University, Paris, France. 5. Department of Biopathology, Institut Curie, PSL Research University, Paris, France. 6. Faculty of Medicine, University of Paris Descartes, Paris, France. 7. Department of Medical Imaging, Institut Curie, PSL Research University, Paris, France. 8. Department of Surgical Oncology, Institut Curie, PSL Research University, Paris, France. 9. Department of Translational Research, Institut Curie, PSL Research University, Paris, France. 10. Department of Ocular Oncology, Institut Curie, PSL Research University, Paris, France.
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.
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.
Authors: Joanna Patrycja Wróblewska; Michał Stefan Lach; Adam Ustaszewski; Katarzyna Kulcenty; Matthew Ibbs; Inga Jagiełło; Wiktoria Maria Suchorska; Andrzej Marszałek Journal: Genes (Basel) Date: 2020-03-02 Impact factor: 4.096
Authors: Shanna Dewaele; Louis Delhaye; Boel De Paepe; Eric James de Bony; Jilke De Wilde; Katrien Vanderheyden; Jasper Anckaert; Nurten Yigit; Justine Nuytens; Eveline Vanden Eynde; Joél Smet; Maxime Verschoore; Fariba Nemati; Didier Decaudin; Manuel Rodrigues; Peihua Zhao; Aart Jochemsen; Eleonora Leucci; Jo Vandesompele; Jo Van Dorpe; Jean-Christophe Marine; Rudy Van Coster; Sven Eyckerman; Pieter Mestdagh Journal: Oncogene Date: 2021-09-10 Impact factor: 9.867