The genomic and transcriptomic landscape of metastastic urothelial cancer.

Humans Receptor, Fibroblast Growth Factor, Type 3 / genetics Transcriptome Mutation Male Female Exome Sequencing Receptor, ErbB-2 / genetics Urinary Bladder Neoplasms / genetics Nectins / genetics Aged Tuberous Sclerosis Complex 1 Protein / genetics Cell Adhesion Molecules / genetics Antigens, Neoplasm / genetics Class I Phosphatidylinositol 3-Kinases / genetics Genomics Middle Aged APOBEC Deaminases / genetics Urothelium / pathology Gene Expression Regulation, Neoplastic Cytidine Deaminase / genetics Neoplasm Metastasis / genetics Aged, 80 and over Carcinoma, Transitional Cell / genetics Urologic Neoplasms / genetics Gene Expression Profiling / methods

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
04 Oct 2024

Historique:

received: 06 03 2024

accepted: 20 09 2024

medline: 5 10 2024

pubmed: 5 10 2024

entrez: 4 10 2024

Statut: epublish

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.

Identifiants

DOI: 10.1038/s41467-024-52915-0 PMID: 39366934

pubmed: 39366934

doi: 10.1038/s41467-024-52915-0

pii: 10.1038/s41467-024-52915-0

doi:

Substances chimiques

Receptor, Fibroblast Growth Factor, Type 3 EC 2.7.10.1

FGFR3 protein, human EC 2.7.10.1

Receptor, ErbB-2 EC 2.7.10.1

ERBB2 protein, human EC 2.7.10.1

PIK3CA protein, human EC 2.7.1.137

TSC1 protein, human 0

Nectins 0

Tuberous Sclerosis Complex 1 Protein 0

Cell Adhesion Molecules 0

Antigens, Neoplasm 0

Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137

APOBEC Deaminases EC 3.5.4.5

Cytidine Deaminase EC 3.5.4.5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

8603

Subventions

Organisme : Agence Nationale de la Recherche (French National Research Agency)

ID : ANR-10-EQPX-03

Organisme : Agence Nationale de la Recherche (French National Research Agency)

ID : ANR-10-INBS-09-08

Informations de copyright

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