Uveal melanoma is a clinically distinct and particularly lethal subtype of melanoma originating from melanocytes in the eye. Here, we performed multi-region DNA sequencing of primary uveal melanomas and their matched metastases from 35 patients. We observed novel driver mutations and established the order in which these and known driver mutations undergo selection. Metastases had genomic alterations distinct from their primary tumors, and metastatic dissemination sometimes occurred early during the development of the primary tumor. Our study offers new insights into the genetics and evolution of this melanoma subtype, providing potential biomarkers for progression and therapy.
Citation: Dogrusöz M, Bagger M, van Duinen SG, et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci. 2017;58:833-842. DOI:10.1167/ iovs.16-20212 PURPOSE. The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system. METHODS.We retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status. Death due to UM metastases was the primary endpoint.RESULTS. In AJCC stage I cases, only patients with monosomy 3 as well as chromosome 8q gain died due to UM metastases (P < 0.001). Among patients with stage II and III tumors, those with monosomy 3 plus gain of chromosome 8q had the worst prognosis, whereas the clinical outcome of those with only one of these aberrations was intermediate (P < 0.001). Patients without monosomy 3 and 8q gain showed favorable prognosis, independent of their tumor's AJCC stage. In cases with monosomy 3, 8q gain, or both, adding AJCC stage improved the predictive value. Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status.CONCLUSIONS. Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic value of the AJCC staging system can be improved by adding information regarding chromosome 3 and 8q status.
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