Nature Communications (Oct 2024)
The genomic and transcriptomic landscape of metastastic urothelial cancer
- Yohann Loriot,
- Maud Kamal,
- Laurene Syx,
- Remy Nicolle,
- Celia Dupain,
- Naoual Menssouri,
- Igor Duquesne,
- Pernelle Lavaud,
- Claudio Nicotra,
- Maud Ngocamus,
- Ludovic Lacroix,
- Lambros Tselikas,
- Gilles Crehange,
- Luc Friboulet,
- Zahra Castel-Ajgal,
- Yann Neuzillet,
- Edith Borcoman,
- Philippe Beuzeboc,
- Grégoire Marret,
- Tom Gutman,
- Jennifer Wong,
- Francois Radvanyi,
- Sylvain Dureau,
- Jean-Yves Scoazec,
- Nicolas Servant,
- Yves Allory,
- Benjamin Besse,
- Fabrice Andre,
- Christophe Le tourneau,
- Christophe Massard,
- Ivan Bieche
Affiliations
- Yohann Loriot
- Gustave Roussy, DITEP, Gustave Roussy
- Maud Kamal
- Department of Drug Development and Innovation (D3i), Institut Curie
- Laurene Syx
- Bioinformatics and Computational Systems Biology of Cancer, Institut Curie, PSL Research University, Mines Paris Tech, INSERM U900
- Remy Nicolle
- Université Paris Cité, Centre de Recherche sur l’Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, F-
- Celia Dupain
- Department of Drug Development and Innovation (D3i), Institut Curie
- Naoual Menssouri
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Igor Duquesne
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Pernelle Lavaud
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Claudio Nicotra
- Gustave Roussy, DITEP, Gustave Roussy
- Maud Ngocamus
- Gustave Roussy, DITEP, Gustave Roussy
- Ludovic Lacroix
- Biopath department, Gustave Roussy
- Lambros Tselikas
- Department of interventional radiology, Gustave Roussy
- Gilles Crehange
- Department of Radiothérapie, Institut Curie, 75005 Paris & 92210 Saint-Cloud
- Luc Friboulet
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Zahra Castel-Ajgal
- Department of Drug Development and Innovation (D3i), Institut Curie
- Yann Neuzillet
- Department of Urology, Foch Hospital
- Edith Borcoman
- Department of Drug Development and Innovation (D3i), Institut Curie
- Philippe Beuzeboc
- Department of Urology, Foch Hospital
- Grégoire Marret
- Department of Drug Development and Innovation (D3i), Institut Curie
- Tom Gutman
- Bioinformatics and Computational Systems Biology of Cancer, Institut Curie, PSL Research University, Mines Paris Tech, INSERM U900
- Jennifer Wong
- Department of Genetics, Institut Curie
- Francois Radvanyi
- UMR144, Institut Curie
- Sylvain Dureau
- Biometry unit, direction of clinical research, Institut Curie
- Jean-Yves Scoazec
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Nicolas Servant
- Bioinformatics and Computational Systems Biology of Cancer, Institut Curie, PSL Research University, Mines Paris Tech, INSERM U900
- Yves Allory
- Department of Pathology, Institut Curie, PSL Research University
- Benjamin Besse
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Fabrice Andre
- INSERM 981, Université Paris-Saclay, Gustave Roussy
- Christophe Le tourneau
- Department of Drug Development and Innovation (D3i), Institut Curie
- Christophe Massard
- Gustave Roussy, DITEP, Gustave Roussy
- Ivan Bieche
- Department of Genetics, Institut Curie
- DOI
- https://doi.org/10.1038/s41467-024-52915-0
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 12
Abstract
Abstract Metastatic urothelial carcinoma (mUC) is a lethal cancer, with limited therapeutic options. Large-scale studies in early settings provided critical insights into the genomic and transcriptomic characteristics of non-metastatic UC. The genomic landscape of mUC remains however unclear. Using Whole Exome (WES) and mRNA sequencing (RNA-seq) performed on metastatic biopsies from 111 patients, we show that driver genomic alterations from mUC were comparable to primary UC (TCGA data). APOBEC, platin, and HRD mutational signatures are the most prevalent in mUC, identified in 56%, 14%, and 9% of mUC samples, respectively. Molecular subtyping using consensus transcriptomic classification in mUC shows enrichment in neuroendocrine subtype. Paired samples analysis reveals subtype heterogeneity and temporal evolution. We identify potential therapeutic targets in 73% of mUC patients, of which FGFR3 (26%), ERBB2 (7%), TSC1 (7%), and PIK3CA (13%) are the most common. NECTIN4 and TACSTD2 are highly expressed regardless of molecular subtypes, FGFR3 alterations and sites of metastases.
