Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours-Reference-Cited by-同舟云学术

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

Published:2020-05-15 Issue:1 Volume:11 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Johansson Peter A.,Brooks Kelly,Newell Felicity,Palmer Jane M.^ORCID,Wilmott James S.,Pritchard Antonia L.,Broit Natasa,Wood Scott,Carlino Matteo S.,Leonard Conrad,Koufariotis Lambros T.,Nathan Vaishnavi^ORCID,Beasley Aaron B.^ORCID,Howlie Madeleine,Dawson Rebecca,Rizos Helen^ORCID,Schmidt Chris W.^ORCID,Long Georgina V.,Hamilton Hayley,Kiilgaard Jens F.^ORCID,Isaacs Timothy,Gray Elin S.^ORCID,Rolfe Olivia J.,Park John J.,Stark Andrew,Mann Graham J.,Scolyer Richard A.^ORCID,Pearson John V.,van Baren Nicolas,Waddell Nicola^ORCID,Wadt Karin W.^ORCID,McGrath Lindsay A.^ORCID,Warrier Sunil K.,Glasson William,Hayward Nicholas K.^ORCID

Abstract

AbstractUveal 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).

Funder

Department of Health | National Health and Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-020-16276-8.pdf

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