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).
Keywords
cancer genomics, genome informatics, melanoma
Document Type
Journal Article
Date of Publication
1-1-2020
Publication Title
Nature Communications
Publisher
Springer Nature
School
School of Medical and Health Sciences
RAS ID
31587
Funders
Funding information available at https://doi.org/10.1007/s00429-020-02071-1
Grant Number
NHMRC Number : 1093017
Grant Link
http://purl.org/au-research/grants/nhmrc/1093017
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Johansson, P. A., Brooks, K., Newell, F., Palmer, J. M., Wilmott, J. S., Pritchard, A. L., ... & Koufariotis, L. T. (2020). Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours. Nature communications, 11(1), Article number: 2408. https://doi.org/10.1038/s41467-020-16276-8