Postdoctoral Scholar,
Gentles Lab/Mackall Lab,
Stanford University

Uveal melanoma (UM) is the most common cancer of the adult eye and manifests as a highly aggressive form in approximately half of the patients. We performed a comprehensive landscape of genetic alterations in UM by integrating copy number alterations, transcriptomic and exome sequencing data across 207 primary UMs.  Focal copy number analysis with the GISTIC algorithm refined the boundaries of chromosomal segments with chromosomal gains or losses and candidate cancer genes within segments of chromosomes 1, 2, 6 and 11 were identified. Using a complementary bioinformatics approach and incorporating data from exome sequencing, additional novel mutations in known dominant UM driver genes (GNAQ, GNA11, BAP1, SF3B1, EIFIAX and CYSLTR2) were identified. An accurate estimate of the frequencies of mutations in each gene were obtained. Finally, integration of data obtained from CNAs with transcriptome data from two datasets reveled two overlapping deleted loci, 6q and 1p36, which have historically been candidate loci for unidentified tumor suppressor genes. In conclusion, this study provides a comprehensive overview of the landscape of genomic alterations in UM and identifying novel candidate genes in regions of CNAs which could provide further insights into tumor development and progression in UMs.