Estimation of the timing of BAP1 mutation in uveal melanoma progression

Abstract Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured....

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Autores principales:	Ogul E. Uner, Thonnie Rose O. See, Eszter Szalai, Hans E. Grossniklaus, Gustav Stålhammar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5fbabffe64414e6caae43261f1a65706
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spelling	oai:doaj.org-article:5fbabffe64414e6caae43261f1a657062021-12-02T17:39:20ZEstimation of the timing of BAP1 mutation in uveal melanoma progression10.1038/s41598-021-88390-62045-2322https://doaj.org/article/5fbabffe64414e6caae43261f1a657062021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88390-6https://doaj.org/toc/2045-2322Abstract Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 μm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.Ogul E. UnerThonnie Rose O. SeeEszter SzalaiHans E. GrossniklausGustav StålhammarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ogul E. Uner Thonnie Rose O. See Eszter Szalai Hans E. Grossniklaus Gustav Stålhammar Estimation of the timing of BAP1 mutation in uveal melanoma progression
description	Abstract Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 μm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.
format	article
author	Ogul E. Uner Thonnie Rose O. See Eszter Szalai Hans E. Grossniklaus Gustav Stålhammar
author_facet	Ogul E. Uner Thonnie Rose O. See Eszter Szalai Hans E. Grossniklaus Gustav Stålhammar
author_sort	Ogul E. Uner
title	Estimation of the timing of BAP1 mutation in uveal melanoma progression
title_short	Estimation of the timing of BAP1 mutation in uveal melanoma progression
title_full	Estimation of the timing of BAP1 mutation in uveal melanoma progression
title_fullStr	Estimation of the timing of BAP1 mutation in uveal melanoma progression
title_full_unstemmed	Estimation of the timing of BAP1 mutation in uveal melanoma progression
title_sort	estimation of the timing of bap1 mutation in uveal melanoma progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5fbabffe64414e6caae43261f1a65706
work_keys_str_mv	AT oguleuner estimationofthetimingofbap1mutationinuvealmelanomaprogression AT thonnieroseosee estimationofthetimingofbap1mutationinuvealmelanomaprogression AT eszterszalai estimationofthetimingofbap1mutationinuvealmelanomaprogression AT hansegrossniklaus estimationofthetimingofbap1mutationinuvealmelanomaprogression AT gustavstalhammar estimationofthetimingofbap1mutationinuvealmelanomaprogression
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Estimation of the timing of BAP1 mutation in uveal melanoma progression

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