Dataset Information

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

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.

SUBMITTER: Rodrigues M

PROVIDER: S-EPMC6990836 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Rodrigues Manuel M Ait Rais Khadija K Salviat Flore F Algret Nathalie N Simaga Fatoumata F Barnhill Raymond R Gardrat Sophie S Servois Vincent V Mariani Pascale P Piperno-Neumann Sophie S Roman-Roman Sergio S Delattre Olivier O Cassoux Nathalie N Savignoni Alexia A Stern Marc-Henri MH Pierron Gaëlle G

JAMA ophthalmology 20200201 2

<h4>Importance</h4>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.<h4>Objective</h4>To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival.<h4>Design, setting, and participants</h4>This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, a ...[more]

PMID: 31895446

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Project description:ImportanceAccuracy of the predicted metastasis-free survival (MFS) by a commercially available gene expression profiling (GEP) test is not known.ObjectiveTo compare the predicted MFS with the observed MFS in patients in this cohort and with those in published studies (published MFS, meta-analysis).Design, setting, and participantsThis cohort study included consecutive patients from the University of Iowa and Cleveland Clinic who were diagnosed with uveal melanoma who underwent prognostic fine-needle aspiration biopsy at the time of primary treatment. Patients were recruited from December 2012 to December 2020. The predicted MFS for patients was extracted from the GEP report. The observed MFS was defined as time to metastasis. Cox proportional hazards models were fit to identify tumor variables impacting MFS in patients with class 2 tumors. The overall estimate of the published MFS was obtained by performing meta-analysis of data from published series. Analysis took place in August 2021.Main outcomes and measuresMFS.ResultsThere were 92 patients from the University of Iowa and 255 patients from the Cleveland Clinic. The mean (SD) age at diagnosis was 59.4 (13.0) years. The median (IQR) follow-up interval was 38.0 (19.0-57.0) months. The observed MFS for patients with class 2 tumor in this cohort (3 years: 67% [95% CI, 59%-77%]; 5 years: 47% [95% CI, 37%-61%]) and in published studies (3 years: 62% [95% CI, 57%-66%]; 5 years: 40% [95% CI, 34%-46%]) were better than those predicted (50% and 28% for 3 and 5 years, respectively). Within patients with class 2 tumor, those with metastasis had larger tumors compared with nonmetastatic tumors (mean largest basal diameter difference, 1.7 [95% CI, 0.5-3.0] mm; P = .01; mean thickness ratio, 1.3 [95% CI, 1.04-1.5]; P = .01, respectively). An increasing tumor size was significantly associated with increased hazard ratio (1.16 [95% CI, 1.06-1.27]; P < .001) of metastasis.Conclusions and relevanceThese findings suggest the predicted MFS for metastatic tumors (class 2) appears to be worse than that observed here and reported by others. Incorporation of tumor size in the prediction model may enhance its accuracy. Adjuvant therapy trials may not be able to rely on predicted MFS to calculate efficacy with a high degree of confidence.

Project description:Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high‑risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high‑grade vs. low‑grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR‑506‑514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA‑mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen‑activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR‑506‑514 cluster, hsa‑miR‑592 and hsa‑miR‑199a‑5p were the most deregulated miRNAs in patients with high‑grade disease compared to those with low‑grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings.

Dataset Information

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

Publications

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

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