Integrated Molecular Analysis of Papillary Renal Cell Carcinoma and Precursor Lesions Unfolds Evolutionary Process from Kidney Progenitor-Like Cells.

Autor:	Saleeb RM; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Farag M; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Ding Q; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Downes M; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Bjarnason G; Division of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Brimo F; Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada., Plant P; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Rotondo F; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Lichner Z; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Finelli A; Division of Urology, Department of Surgery, University Health Network, Toronto, Ontario, Canada., Yousef GM; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: george.yousef@sickkids.ca.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2019 Oct; Vol. 189 (10), pp. 2046-2060. Date of Electronic Publication: 2019 Aug 02.
DOI:	10.1016/j.ajpath.2019.07.002
Abstrakt:	Papillary renal cell carcinoma (PRCC) is the most common type of RCC in end-stage kidney disease (ESKD). Papillary adenoma (PA) is a small benign lesion morphologically similar to PRCC and is suggested to be its precursor. PA is also prevalent in ESKD. The evolution of PAs to PRCCs and their relationship to ESKD are poorly understood. A total of 140 PAs, normal kidneys, ESKDs, and PRCCs were analyzed. Previously described markers of renal tubular progenitor cells were analyzed using immunohistochemistry and quantified with digital analysis. Progenitor cells were significantly increased in ESKD (P < 0.0001) and PAs (P = 0.02) in comparison with the normal kidney. Pathway analysis using global miRNA and chromosomal copy number variations revealed a common developmental theme between PA and the PRCCs. Whole exome sequencing showed a KMT2C-specific pathogenic mutation among all PAs and PRCCs. KMT2C is a chromosome 7 epigenetic regulator implicated in development and oncogenesis. Collectively, results show possible connection of PRCCs to PA and the progenitor-like cell population, which are increased in response to renal tubular injury. In addition, each PRCC histologic subtype had its own set of mutational changes, indicating divergence from a common precursor. The study reports previously unknown biological aspects of PRCC development and could influence current surveillance criteria and early detection strategies of PRCC tumors. (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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