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 KiilgaardTimothy 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

95 Citationer (Scopus)

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).

Originalsprog	Engelsk
Artikelnummer	2408
Tidsskrift	Nature Communications
Vol/bind	11
Udgave nummer	1
Sider (fra-til)	2408
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-020-16276-8
Status	Udgivet - 15 maj 2020

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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), 2408. Artikel 2408. https://doi.org/10.1038/s41467-020-16276-8

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, bind 11, nr. 1, 2408, s. 2408. https://doi.org/10.1038/s41467-020-16276-8

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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).",

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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

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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).

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

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