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Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship

We used the fact that patients with non-muscle invasive bladder tumors show local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosoma...

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Autores principales: Marzouka, Nour-Al-Dain, Lindgren, David, Eriksson, Pontus, Sjödahl, Gottfrid, Bernardo, Carina, Liedberg, Fredrik, Axelson, Håkan, Höglund, Mattias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658206/
https://www.ncbi.nlm.nih.gov/pubmed/33177554
http://dx.doi.org/10.1038/s41598-020-75854-4
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author Marzouka, Nour-Al-Dain
Lindgren, David
Eriksson, Pontus
Sjödahl, Gottfrid
Bernardo, Carina
Liedberg, Fredrik
Axelson, Håkan
Höglund, Mattias
author_facet Marzouka, Nour-Al-Dain
Lindgren, David
Eriksson, Pontus
Sjödahl, Gottfrid
Bernardo, Carina
Liedberg, Fredrik
Axelson, Håkan
Höglund, Mattias
author_sort Marzouka, Nour-Al-Dain
collection PubMed
description We used the fact that patients with non-muscle invasive bladder tumors show local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosomal aberrations may be detected in one tumor, only to be undetected in a recurrent tumor. By analyses of incompatible changes i.e., genomic alterations that cannot be reversed, we show that almost all tumors from a single patient may show such changes, thus the tumors cannot have originated from each other. As recurring tumors share both genomic alterations and driver gene mutations, these must have been present in the urothelium in periods with no tumor growth. We present a model that includes a growing and evolving field of urothelial cells that occasionally, and locally, produce bursts of cellular growth leading to overt tumors.
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spelling pubmed-76582062020-11-12 Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship Marzouka, Nour-Al-Dain Lindgren, David Eriksson, Pontus Sjödahl, Gottfrid Bernardo, Carina Liedberg, Fredrik Axelson, Håkan Höglund, Mattias Sci Rep Article We used the fact that patients with non-muscle invasive bladder tumors show local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosomal aberrations may be detected in one tumor, only to be undetected in a recurrent tumor. By analyses of incompatible changes i.e., genomic alterations that cannot be reversed, we show that almost all tumors from a single patient may show such changes, thus the tumors cannot have originated from each other. As recurring tumors share both genomic alterations and driver gene mutations, these must have been present in the urothelium in periods with no tumor growth. We present a model that includes a growing and evolving field of urothelial cells that occasionally, and locally, produce bursts of cellular growth leading to overt tumors. Nature Publishing Group UK 2020-11-11 /pmc/articles/PMC7658206/ /pubmed/33177554 http://dx.doi.org/10.1038/s41598-020-75854-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Marzouka, Nour-Al-Dain
Lindgren, David
Eriksson, Pontus
Sjödahl, Gottfrid
Bernardo, Carina
Liedberg, Fredrik
Axelson, Håkan
Höglund, Mattias
Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title_full Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title_fullStr Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title_full_unstemmed Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title_short Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
title_sort recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658206/
https://www.ncbi.nlm.nih.gov/pubmed/33177554
http://dx.doi.org/10.1038/s41598-020-75854-4
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