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

Peter A JohanssonKelly BrooksFelicity NewellJane M PalmerJames S WilmottAntonia L PritchardNatasa BroitScott WoodMatteo S CarlinoConrad LeonardLambros T KoufariotisVaishnavi NathanAaron B BeasleyMadeleine HowlieRebecca DawsonHelen RizosChris W SchmidtGeorgina V LongHayley HamiltonJens Folke KiilgaardTimothy IsaacsElin Solomonovna GrayOlivia J RolfeJohn J ParkAndrew StarkGraham J MannRichard A ScolyerJohn V PearsonNicolas van BarenNicola WaddellKarin A W WadtLindsay A McGrathSunil K WarrierWilliam GlassonNicholas K Hayward
Published in: Nature communications (2020)
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).
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