1. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.
- Author
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Johansson PA, Brooks K, Newell F, Palmer JM, Wilmott JS, Pritchard AL, Broit N, Wood S, Carlino MS, Leonard C, Koufariotis LT, Nathan V, Beasley AB, Howlie M, Dawson R, Rizos H, Schmidt CW, Long GV, Hamilton H, Kiilgaard JF, Isaacs T, Gray ES, Rolfe OJ, Park JJ, Stark A, Mann GJ, Scolyer RA, Pearson JV, van Baren N, Waddell N, Wadt KW, McGrath LA, Warrier SK, Glasson W, and Hayward NK
- Subjects
- Cell Line, Tumor, Chromosome Aberrations, Computational Biology, DNA Mutational Analysis, Disease Progression, Disease-Free Survival, Gene Dosage, Genome, Human, Genomics, Humans, Kaplan-Meier Estimate, Markov Chains, Melanocytes metabolism, Mutation, Phenotype, Prognosis, Tumor Suppressor Protein p53 genetics, Ultraviolet Rays, Iris Neoplasms genetics, Iris Neoplasms pathology, Melanoma genetics, Melanoma pathology, Uveal Neoplasms genetics, Uveal Neoplasms pathology
- Abstract
Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).
- Published
- 2020
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