TY - JOUR
T1 - Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas
AU - Malouf, Gabriel G.
AU - Compérat, Eva
AU - Yao, Hui
AU - Mouawad, Roger
AU - Lindner, Veronique
AU - Rioux-Leclercq, Nathalie
AU - Verkarre, Virginie
AU - Leroy, Xavier
AU - Dainese, Linda
AU - Classe, Marion
AU - Descotes, Jean Luc
AU - Barthelemy, Philippe
AU - Yacoub, Mokrane
AU - Rouprêt, Morgan
AU - Bernhard, Jean Christophe
AU - Creighton, Chad J.
AU - Spano, Jean Philippe
AU - Su, Xiaoping
AU - Khayat, David
N1 - Funding Information:
In memory of Yves Carcelle. The authors thank all the patients and their families who contributes to the study. They also acknowledge biobanks from participating institutions including CHU Rennes, Necker Hospital, Pitié-Salpêtrière Hospital, CHU Grenoble, CHU Bordeaux and CHU Strasbourg. This work was supported by la Fondation AVEC (G.G.M., R.M. and D.K.) and NIH CA125123 (C.J.C).
PY - 2016/8/3
Y1 - 2016/8/3
N2 - 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.
AB - 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.
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U2 - 10.1038/srep30988
DO - 10.1038/srep30988
M3 - Article
C2 - 27484008
AN - SCOPUS:84982740590
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 30988
ER -