Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas.
Fiche publication
Date publication
août 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARTHELEMY Philippe, Dr LINDNER Véronique, Pr MALOUF Gabriel
Tous les auteurs :
Malouf GG, Compérat E, Yao H, Mouawad R, Lindner V, Rioux-Leclercq N, Verkarre V, Leroy X, Dainese L, Classe M, Descotes JL, Barthelemy P, Yacoub M, Rouprêt M, Bernhard JC, Creighton CJ, Spano JP, Su X, Khayat D
Lien Pubmed
Résumé
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.
Mots clés
Adolescent, Adult, Aged, Biomarkers, Tumor, genetics, Carcinoma, Renal Cell, genetics, Female, Humans, Kidney Neoplasms, genetics, Male, Middle Aged, Transcriptome, Urologic Neoplasms, genetics, Young Adult
Référence
Sci Rep. 2016 Aug;6:30988