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

Nat Commun. 2020 May 15;11(1):2408. doi: 10.1038/s41467-020-16276-8.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromosome Aberrations
  • Computational Biology
  • DNA Mutational Analysis
  • Disease Progression
  • Disease-Free Survival
  • Gene Dosage
  • Genome, Human
  • Genomics
  • Humans
  • Iris Neoplasms / genetics*
  • Iris Neoplasms / pathology*
  • Kaplan-Meier Estimate
  • Markov Chains
  • Melanocytes / metabolism
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Mutation
  • Phenotype
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics
  • Ultraviolet Rays
  • Uveal Neoplasms / genetics*
  • Uveal Neoplasms / pathology*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Uveal melanoma