Nature communications · 2024
The genomic and transcriptomic landscape of metastastic urothelial cancer.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Loriot Yohann, Kamal Maud, Syx Laurene, Nicolle Remy, Dupain Celia, Menssouri Naoual, Duquesne Igor, Lavaud Pernelle, Nicotra Claudio, Ngocamus Maud, Lacroix Ludovic, Tselikas Lambros, Crehange Gilles, Friboulet Luc, Castel-Ajgal Zahra, Neuzillet Yann, Borcoman Edith, Beuzeboc Philippe, Marret Grégoire, Gutman Tom, Wong Jennifer, Radvanyi Francois, Dureau Sylvain, Scoazec Jean-Yves, Servant Nicolas, Allory Yves, Besse Benjamin, Andre Fabrice, Le Tourneau Christophe, Massard Christophe, Bieche Ivan
Аннотация
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.
Предметные рубрики MeSH
HumansReceptor, Fibroblast Growth Factor, Type 3TranscriptomeMutationMaleFemaleExome SequencingErb-b2 Receptor Tyrosine KinasesUrinary Bladder NeoplasmsNectinsAgedTuberous Sclerosis Complex 1 ProteinCell Adhesion MoleculesAntigens, NeoplasmClass I Phosphatidylinositol 3-KinasesGenomicsMiddle AgedAPOBEC DeaminasesUrotheliumGene Expression Regulation, NeoplasticCytidine DeaminaseNeoplasm MetastasisAged, 80 and overCarcinoma, Transitional CellUrologic NeoplasmsGene Expression Profiling