Class2, 1p loss, 8q gain uveal melanoma: a case report

Purpose Metastatic spread of uveal melanoma (UM) is associated with epithelial‐mesenchymal transition (EMT). This process is not sufficiently investigated in UM due to its neuroectodermal origin. Herein we present a case study of 1p loss, 8q gain in a locally advanced UM patient enrolled after the onset of metastatic disease. Methods UM‐specific chromosomal rearrangements were assessed by MLPA, transcriptomic analysis using the Agilent microarray platform. Vital tumor cells were injected subcutaneously into NSG® mice to develop patient‐derived xenografts (PDX). Nine hot‐spot mutations in four genes (GNA11, GNAQ, PLCβ4, and CYSLTR2) were investigated by digital droplet PCR (ddPCR). Results The tumor and the heterogeneous tumor‐bearing mass in the right orbit were confirmed as a malignant neoplasm with an unfavorable immunophenotype, poor prognosis Class 2 gene expression profile, 1p loss, and 8q gain. GNA11 p.Q209L mutation with high plasmatic ctDNA copy numbers (n = 108/ul) was found by ddPCR. Despite the lack of monosomy 3, PDXs were successfully derived, with high vimentin expression in the second passage. Conclusions 1p loss and 8q gain were associated with the distinct gene expression pattern of EMT‐associated genes, unfavorable phenotype, and development of PDX. This work was supported by APVV‐17‐0369 and VEGA 1/0395/21 grants.