title: Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas.
abstract: Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes. We discovered that CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules. Hierarchical unsupervised clustering reveals that the CDC signature is closer to that of other RCC subtypes than to UTUC, which is similar to that of bladder carcinoma. CDC is characterized by a metabolic shift, with impairment of oxidoreductase activity, pyruvate metabolism and the tricarboxlyic acid cycle, as well as an immunogenic response consistent with increased tumor infiltrating lymphocytes, particularly within metastatic cases. In addition, pathways differentially altered between CDC and UTUC point to a basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. We conclude that CDC harbors a pathognomonic transcriptomic signature characterized by immunogenic and a metabolic aberrations, indicating that targeting these processes might provide therapeutic options for patients.
authors.affiliation: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Malouf
authors.affiliation: Department of Medical Pathology Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.affiliation: Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Mouawad
authors.affiliation: Department of Pathology, CHU Strasbourg, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Lindner
authors.affiliation: Department of Pathology, CHU Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, University Paris V, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.affiliation: Department of Pathology, CHU Lille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leroy
authors.affiliation: Department of Pathology, Trousseau Hospital, Paris, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Dainese
authors.affiliation: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Classe
authors.affiliation: Department of Urology, CHU Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Descotes
authors.affiliation: Department of Medical Oncology, CHU Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthelemy
authors.affiliation: Department of Pathology, CHU Bordeaux, France.|UroCCR French Network for Research on Kidney Cancer (UroCCR), Bordeaux, France.
authors.forename: Mokrane
authors.initials: M
authors.lastname: Yacoub
authors.affiliation: Departments of Medical Urology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: UroCCR French Network for Research on Kidney Cancer (UroCCR), Bordeaux, France.|Department of Urology, CHU Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bernhard
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Spano
authors.affiliation: Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, University Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, 75013, France.
authors.forename: David
authors.initials: D
authors.lastname: Khayat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor