GNAQ

Gene

Ultraviolet radiation

Ciliary body

Neuroscience

Biology

BAP1

Retina

Computer security

Mutation

Cancer research

Computer science

Radiochemistry

Computational biology

Choroid

Melanoma

Genetics

IRIS (biosensor)

Signature (topology)

Germline mutation

Genome

Mathematics

Artificial intelligence

Geometry

Medicine

Chemistry

Uvea

Biometrics

Pathology

Nature Communications

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).

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours