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

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

doi:10.1038/s41467-020-16276-8

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

Peter A. Johansson
, Kelly Brooks
, Felicity Newell
, Jane M. Palmer
, James S. Wilmott
, Antonia L. Pritchard
, Natasa Broit
, Scott Wood
, Matteo S. Carlino
, Conrad Leonard
, Lambros T. Koufariotis
, Vaishnavi Nathan
, Aaron B. Beasley
, Madeleine Howlie
, Rebecca Dawson
, Helen Rizos
, Chris W. Schmidt
, Georgina V. Long
, Hayley Hamilton
, Jens F. Kiilgaard

Timothy Isaacs, Elin S. Gray, Olivia J. Rolfe, John J. Park, Andrew Stark, Graham J. Mann, Richard A. Scolyer, John V. Pearson, Nicolas Van Baren, Nicola Waddell, Karin W. Wadt, Lindsay A. Mcgrath, Sunil K. Warrier, William Glasson, Nicholas K. Hayward

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Résumé

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).

langue originale	English
Numéro d'article	2408 (2020)
Pages (de - à)	1-8
Nombre de pages	8
journal	Nature Communications
Volume	11
Les DOIs	https://doi.org/10.1038/s41467-020-16276-8
état	Published - 15 mai 2020

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10.1038/s41467-020-16276-8License: CC BY

Johansson_Whole genome landscapes of UM show a UV radiation signature in iris tumoursAccepted author manuscript, 61,4 KB
s41467-020-16276-8
© The Author(s) 2020.
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http://www.nature.com/articles/s41467-020-16276-8

Antonia Pritchard
- antonia.pritcharduhi.acuk
- Division of Biomedical Sciences - Reader in Genetics and Immunology
- Melanoma Research Group
personne: Academic - Research and Teaching or Research only

Contient cette citation

Johansson, P. A., Brooks, K., Newell, F., Palmer, J. M., Wilmott, J. S., Pritchard, A. L., Broit, N., Wood, S., Carlino, M. S., Leonard, C., Koufariotis, L. T., Nathan, V., Beasley, A. B., Howlie, M., Dawson, R., Rizos, H., Schmidt, C. W., Long, G. V., Hamilton, H., ... Hayward, N. K. (2020). Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours. Nature Communications, 11, 1-8. Article 2408 (2020). https://doi.org/10.1038/s41467-020-16276-8

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title = "Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours",

abstract = "Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, \textasciitilde{}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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author = "Johansson, \{Peter A.\} and Kelly Brooks and Felicity Newell and Palmer, \{Jane M.\} and Wilmott, \{James S.\} and Pritchard, \{Antonia L.\} and Natasa Broit and Scott Wood and Carlino, \{Matteo S.\} and Conrad Leonard and Koufariotis, \{Lambros T.\} and Vaishnavi Nathan and Beasley, \{Aaron B.\} and Madeleine Howlie and Rebecca Dawson and Helen Rizos and Schmidt, \{Chris W.\} and Long, \{Georgina V.\} and Hayley Hamilton and Kiilgaard, \{Jens F.\} and Timothy Isaacs and Gray, \{Elin S.\} and Rolfe, \{Olivia J.\} and Park, \{John J.\} and Andrew Stark and Mann, \{Graham J.\} and Scolyer, \{Richard A.\} and Pearson, \{John V.\} and \{Van Baren\}, Nicolas and Nicola Waddell and Wadt, \{Karin W.\} and Mcgrath, \{Lindsay A.\} and Warrier, \{Sunil K.\} and William Glasson and Hayward, \{Nicholas K.\}",

note = "{\textcopyright} The Author(s) 2020",

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Johansson, PA, Brooks, K, Newell, F, Palmer, JM, Wilmott, JS, Pritchard, AL, Broit, N, Wood, S, Carlino, MS, Leonard, C, Koufariotis, LT, Nathan, V, Beasley, AB, Howlie, M, Dawson, R, Rizos, H, Schmidt, CW, Long, GV, Hamilton, H, Kiilgaard, JF, Isaacs, T, Gray, ES, Rolfe, OJ, Park, JJ, Stark, A, Mann, GJ, Scolyer, RA, Pearson, JV, Van Baren, N, Waddell, N, Wadt, KW, Mcgrath, LA, Warrier, SK, Glasson, W & Hayward, NK 2020, 'Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours', Nature Communications, VOL. 11, 2408 (2020), p. 1-8. https://doi.org/10.1038/s41467-020-16276-8

TY - JOUR

T1 - Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

AU - Johansson, Peter A.

AU - Brooks, Kelly

AU - Newell, Felicity

AU - Palmer, Jane M.

AU - Wilmott, James S.

AU - Pritchard, Antonia L.

AU - Broit, Natasa

AU - Wood, Scott

AU - Carlino, Matteo S.

AU - Leonard, Conrad

AU - Koufariotis, Lambros T.

AU - Nathan, Vaishnavi

AU - Beasley, Aaron B.

AU - Howlie, Madeleine

AU - Dawson, Rebecca

AU - Rizos, Helen

AU - Schmidt, Chris W.

AU - Long, Georgina V.

AU - Hamilton, Hayley

AU - Kiilgaard, Jens F.

AU - Isaacs, Timothy

AU - Gray, Elin S.

AU - Rolfe, Olivia J.

AU - Park, John J.

AU - Stark, Andrew

AU - Mann, Graham J.

AU - Scolyer, Richard A.

AU - Pearson, John V.

AU - Van Baren, Nicolas

AU - Waddell, Nicola

AU - Wadt, Karin W.

AU - Mcgrath, Lindsay A.

AU - Warrier, Sunil K.

AU - Glasson, William

AU - Hayward, Nicholas K.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - 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).

AB - 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).

KW - 3ref2021

U2 - 10.1038/s41467-020-16276-8

DO - 10.1038/s41467-020-16276-8

M3 - Article

SN - 2041-1723

VL - 11

SP - 1

EP - 8

JO - Nature Communications

JF - Nature Communications

M1 - 2408 (2020)

ER -

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

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