Supplemental Digital Content is available in the text.,The overall survival (OS) of patients with metastatic uveal melanoma is short, the evidence for effectiveness of treatments is limited, and no consensus on the choice of treatment exists.,We aimed to advance interpretation of OS as an outcome by pooling peer-reviewed data.,The design is a systematic review and meta-analysis.,We searched PubMed from 1 January 1980, to 29 March 2017, for articles reporting patient-level survival in Kaplan-Meier or numerical form.,We digitized survival graphs, pooled individual survival times, calculated median OS by treatment modality, and compared each modality by the log-rank test and Cox regression using conventional chemotherapy (CHT) as a reference.,Individual-level data were obtained from 78 articles with 2494 patients.,The median OS across all treatment modalities was 1.07 years (range: 0.59-2.50 years).,Pooled OS reported after isolated hepatic perfusion [median OS: 1.34 years; hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.87-0.97, P = 0.0040], immunoembolization (median OS: 1.63; HR: 0.97, 95% CI: 0.95-1.00, P = 0.0080), and surgery (median OS: 1.43; HR: 0.94, 95% CI: 0.92-0.96, P < 0.0001) was longer, and after checkpoint inhibitor shorter (median OS: 0.59; HR: 1.13, 95% CI: 1.06-1.20, P < 0.0001) than after CHT (median OS: 0.91 years), but subject to identifiable confounding factors.,OS following other modalities did not differ from CHT.,Reported OS was unassociated with the decade of publication, but depended on the percentage of first-line treated patients.,Our results suggest no clinically significant difference in OS by treatment modality or decade.,Most of the difference in reported OS likely is attributable to surveillance, selection, and publication bias rather than treatment-related prolongation.,Our pooled data provide benchmarks for future trials.
Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading.,Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event.,This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively.,Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors.,Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma.,Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance.,The key regulators that allow transition from proliferative to invasive phenotype in melanoma cells have not been identified yet.,The authors perform chromatin and transcriptome profiling followed by comprehensive bioinformatics analysis identifying new candidate regulators for two distinct cell states of melanoma.