Multiregional genetic evolution of metastatic uveal melanoma

Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly u...

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Autores principales:	Daniel A. Rodriguez, Jessica Yang, Michael A. Durante, Alexander N. Shoushtari, Stergios J. Moschos, Kazimierz O. Wrzeszczynski, J. William Harbour, Richard D. Carvajal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/a14dce398f0e41c38acdb3290d8128a5
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spelling	oai:doaj.org-article:a14dce398f0e41c38acdb3290d8128a52021-12-02T15:10:36ZMultiregional genetic evolution of metastatic uveal melanoma10.1038/s41525-021-00233-52056-7944https://doaj.org/article/a14dce398f0e41c38acdb3290d8128a52021-08-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00233-5https://doaj.org/toc/2056-7944Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.Daniel A. RodriguezJessica YangMichael A. DuranteAlexander N. ShoushtariStergios J. MoschosKazimierz O. WrzeszczynskiJ. William HarbourRichard D. CarvajalNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Daniel A. Rodriguez Jessica Yang Michael A. Durante Alexander N. Shoushtari Stergios J. Moschos Kazimierz O. Wrzeszczynski J. William Harbour Richard D. Carvajal Multiregional genetic evolution of metastatic uveal melanoma
description	Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.
format	article
author	Daniel A. Rodriguez Jessica Yang Michael A. Durante Alexander N. Shoushtari Stergios J. Moschos Kazimierz O. Wrzeszczynski J. William Harbour Richard D. Carvajal
author_facet	Daniel A. Rodriguez Jessica Yang Michael A. Durante Alexander N. Shoushtari Stergios J. Moschos Kazimierz O. Wrzeszczynski J. William Harbour Richard D. Carvajal
author_sort	Daniel A. Rodriguez
title	Multiregional genetic evolution of metastatic uveal melanoma
title_short	Multiregional genetic evolution of metastatic uveal melanoma
title_full	Multiregional genetic evolution of metastatic uveal melanoma
title_fullStr	Multiregional genetic evolution of metastatic uveal melanoma
title_full_unstemmed	Multiregional genetic evolution of metastatic uveal melanoma
title_sort	multiregional genetic evolution of metastatic uveal melanoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a14dce398f0e41c38acdb3290d8128a5
work_keys_str_mv	AT danielarodriguez multiregionalgeneticevolutionofmetastaticuvealmelanoma AT jessicayang multiregionalgeneticevolutionofmetastaticuvealmelanoma AT michaeladurante multiregionalgeneticevolutionofmetastaticuvealmelanoma AT alexandernshoushtari multiregionalgeneticevolutionofmetastaticuvealmelanoma AT stergiosjmoschos multiregionalgeneticevolutionofmetastaticuvealmelanoma AT kazimierzowrzeszczynski multiregionalgeneticevolutionofmetastaticuvealmelanoma AT jwilliamharbour multiregionalgeneticevolutionofmetastaticuvealmelanoma AT richarddcarvajal multiregionalgeneticevolutionofmetastaticuvealmelanoma
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Multiregional genetic evolution of metastatic uveal melanoma

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