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The genomic and transcriptomic landscape of metastastic urothelial cancer

Author

Listed:
  • Yohann Loriot

    (Gustave Roussy
    Gustave Roussy
    Gustave Roussy)

  • Maud Kamal

    (Institut Curie)

  • Laurene Syx

    (INSERM U900)

  • Remy Nicolle
  • Celia Dupain

    (Institut Curie)

  • Naoual Menssouri

    (Gustave Roussy)

  • Igor Duquesne

    (Gustave Roussy)

  • Pernelle Lavaud

    (Gustave Roussy)

  • Claudio Nicotra

    (Gustave Roussy)

  • Maud Ngocamus

    (Gustave Roussy)

  • Ludovic Lacroix

    (Gustave Roussy)

  • Lambros Tselikas

    (Gustave Roussy)

  • Gilles Crehange

    (75005 Paris & 92210 Saint-Cloud)

  • Luc Friboulet

    (Gustave Roussy
    Gustave Roussy)

  • Zahra Castel-Ajgal

    (Institut Curie)

  • Yann Neuzillet

    (Foch Hospital)

  • Edith Borcoman

    (Institut Curie)

  • Philippe Beuzeboc

    (Foch Hospital)

  • Grégoire Marret

    (Institut Curie)

  • Tom Gutman

    (INSERM U900)

  • Jennifer Wong

    (Institut Curie)

  • Francois Radvanyi

    (Institut Curie)

  • Sylvain Dureau

    (Institut Curie)

  • Jean-Yves Scoazec

    (Gustave Roussy
    Gustave Roussy)

  • Nicolas Servant

    (INSERM U900)

  • Yves Allory

    (PSL Research University)

  • Benjamin Besse

    (Gustave Roussy
    Gustave Roussy)

  • Fabrice Andre

    (Gustave Roussy
    Gustave Roussy)

  • Christophe tourneau

    (Institut Curie
    INSERM U900)

  • Christophe Massard

    (Gustave Roussy)

  • Ivan Bieche

    (Institut Curie
    Université Paris Cité)

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.

Suggested Citation

  • Yohann Loriot & Maud Kamal & Laurene Syx & Remy Nicolle & Celia Dupain & Naoual Menssouri & Igor Duquesne & Pernelle Lavaud & Claudio Nicotra & Maud Ngocamus & Ludovic Lacroix & Lambros Tselikas & Gil, 2024. "The genomic and transcriptomic landscape of metastastic urothelial cancer," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52915-0
    DOI: 10.1038/s41467-024-52915-0
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    References listed on IDEAS

    as
    1. Aram Vosoughi & Tuo Zhang & Kyrillus S. Shohdy & Panagiotis J. Vlachostergios & David C. Wilkes & Bhavneet Bhinder & Scott T. Tagawa & David M. Nanus & Ana M. Molina & Himisha Beltran & Cora N. Sternb, 2020. "Common germline-somatic variant interactions in advanced urothelial cancer," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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