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Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship

Marzouka, Nour Al Dain LU ; Lindgren, David LU ; Eriksson, Pontus LU ; Sjödahl, Gottfrid LU ; Bernardo, Carina LU orcid ; Liedberg, Fredrik LU ; Axelson, Håkan LU and Höglund, Mattias LU (2020) In Scientific Reports 10(1).
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... (More)

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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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
19539
publisher
Nature Publishing Group
external identifiers
  • scopus:85095851705
  • pmid:33177554
ISSN
2045-2322
DOI
10.1038/s41598-020-75854-4
language
English
LU publication?
yes
id
bcf6da3b-8177-46f5-b112-e1f6873e318b
date added to LUP
2020-12-09 14:52:09
date last changed
2024-05-01 22:38:01
@article{bcf6da3b-8177-46f5-b112-e1f6873e318b,
  abstract     = {{<p>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.</p>}},
  author       = {{Marzouka, Nour Al Dain and Lindgren, David and Eriksson, Pontus and Sjödahl, Gottfrid and Bernardo, Carina and Liedberg, Fredrik and Axelson, Håkan and Höglund, Mattias}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-75854-4}},
  doi          = {{10.1038/s41598-020-75854-4}},
  volume       = {{10}},
  year         = {{2020}},
}