The genomic and transcriptomic landscape of metastastic urothelial cancer

Yohann Loriot; Maud Kamal; Laurene Syx; Remy Nicolle; Celia Dupain; Naoual Mensourri; 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

doi:10.1038/s41467-024-52915-0

The genomic and transcriptomic landscape of metastastic urothelial cancer

Yohann Loriot, Maud Kamal, Laurene Syx, Remy Nicolle, Celia Dupain, Naoual Mensourri, 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 GutmanJennifer Wong, Francois Radvanyi, Sylvain Dureau, Jean Yves Scoazec, Nicolas Servant, Yves Allory, Benjamin Besse, Fabrice Andre, Christophe Le tourneau, Christophe Massard, Ivan Bieche

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

2 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	8603
journal	Nature Communications
Volume	15
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41467-024-52915-0
état	Publié - 1 déc. 2024

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10.1038/s41467-024-52915-0

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Loriot, Y., Kamal, M., Syx, L., Nicolle, R., Dupain, C., Mensourri, N., Duquesne, I., Lavaud, P., Nicotra, C., Ngocamus, M., Lacroix, L., Tselikas, L., Crehange, G., Friboulet, L., Castel-Ajgal, Z., Neuzillet, Y., Borcoman, E., Beuzeboc, P., Marret, G., ... Bieche, I. (2024). The genomic and transcriptomic landscape of metastastic urothelial cancer. Nature Communications, 15(1), Article 8603. https://doi.org/10.1038/s41467-024-52915-0

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title = "The genomic and transcriptomic landscape of metastastic urothelial cancer",

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.",

author = "Yohann Loriot and Maud Kamal and Laurene Syx and Remy Nicolle and Celia Dupain and Naoual Mensourri and Igor Duquesne and Pernelle Lavaud and Claudio Nicotra and Maud Ngocamus and Ludovic Lacroix and Lambros Tselikas and Gilles Crehange and Luc Friboulet and Zahra Castel-Ajgal and Yann Neuzillet and Edith Borcoman and Philippe Beuzeboc and Gr{\'e}goire Marret and Tom Gutman and Jennifer Wong and Francois Radvanyi and Sylvain Dureau and Scoazec, {Jean Yves} and Nicolas Servant and Yves Allory and Benjamin Besse and Fabrice Andre and {Le tourneau}, Christophe and Christophe Massard and Ivan Bieche",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

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Loriot, Y, Kamal, M, Syx, L, Nicolle, R, Dupain, C, Mensourri, N, Duquesne, I, Lavaud, P, Nicotra, C, Ngocamus, M, Lacroix, L, Tselikas, L, Crehange, G, Friboulet, L, Castel-Ajgal, Z, Neuzillet, Y, Borcoman, E, Beuzeboc, P, Marret, G, Gutman, T, Wong, J, Radvanyi, F, Dureau, S, Scoazec, JY, Servant, N, Allory, Y, Besse, B, Andre, F, Le tourneau, C, Massard, C & Bieche, I 2024, 'The genomic and transcriptomic landscape of metastastic urothelial cancer', Nature Communications, VOL. 15, Numéro 1, 8603. https://doi.org/10.1038/s41467-024-52915-0

TY - JOUR

T1 - The genomic and transcriptomic landscape of metastastic urothelial cancer

AU - Loriot, Yohann

AU - Kamal, Maud

AU - Syx, Laurene

AU - Nicolle, Remy

AU - Dupain, Celia

AU - Mensourri, Naoual

AU - Duquesne, Igor

AU - Lavaud, Pernelle

AU - Nicotra, Claudio

AU - Ngocamus, Maud

AU - Lacroix, Ludovic

AU - Tselikas, Lambros

AU - Crehange, Gilles

AU - Friboulet, Luc

AU - Castel-Ajgal, Zahra

AU - Neuzillet, Yann

AU - Borcoman, Edith

AU - Beuzeboc, Philippe

AU - Marret, Grégoire

AU - Gutman, Tom

AU - Wong, Jennifer

AU - Radvanyi, Francois

AU - Dureau, Sylvain

AU - Scoazec, Jean Yves

AU - Servant, Nicolas

AU - Allory, Yves

AU - Besse, Benjamin

AU - Andre, Fabrice

AU - Le tourneau, Christophe

AU - Massard, Christophe

AU - Bieche, Ivan

PY - 2024/12/1

Y1 - 2024/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-024-52915-0

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