Identification of genomic variants associated with Uveal Melanoma by exome sequencing of a patient and controls

Uveal Melanoma (UM) is a distinct subtype of melanoma. It is the most common primary intraocular malignancy of the eye in the western world. Although a limited number of reports are available on genomic alterations in UM among Caucasian patients, in spite of significant differences between epidemiological and clinical features of UM among Asian Indians and Caucasians, no data on genomic alterations are available on Asian Indian patients. In our present study we have identified Somatic mutations in a UM patient without metastasis from India, by comparing the exome sequencing data of the UM patient and that of two control individuals with non-neoplastic blind eyes. Somatic mutations, putatively causal for UM, were identified in GNAQ, SF3B1 and SOX10. Somatic mutations in GNAQ and SF3B1 genes were probable drivers of UM in the Indian patient, as were also earlier reported in some Caucasian patients. In addition, a novel frame shift deletion in exon 4 of the SOX10 gene, which encodes a transcription factor that acts upstream of Microphthalmia-associated transcription factor (MITF) and synergizes with MITF, reportedly have an essential role in melanocyte development and pigmentation, likely plays a role in the development and progression of UM.