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Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship.


ABSTRACT: 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.

SUBMITTER: Marzouka NA 

PROVIDER: S-EPMC7658206 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship.

Marzouka Nour-Al-Dain NA   Lindgren David D   Eriksson Pontus P   Sjödahl Gottfrid G   Bernardo Carina C   Liedberg Fredrik F   Axelson Håkan H   Höglund Mattias M  

Scientific reports 20201111 1


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 t  ...[more]

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