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

Integrated Molecular Analysis of Papillary Renal Cell Carcinoma and Precursor Lesions Unfolds Evolutionary Process from Kidney Progenitor-Like Cells. Am J Pathol. 2019 Aug 02;: Authors: Saleeb RM, Farag M, Ding Q, Downes M, Bjarnason G, Brimo F, Plant P, Rotondo F, Lichner Z, Finelli A, Yousef GM Abstract 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 by some to be its precursor. PA is also very prevalent in ESKD. The evolution of PAs to PRCCs and their relationship to ESKD is poorly understood. One-hundred and forty PAs, normal kidneys, ESKDs, and PRCCs were analyzed. Previously described markers of renal tubular progenitor cells were performed using immunohistochemistry and quantified with digital analysis (n=140). Progenitor cells were significantly increased in ESKD (P < 0.0001) and PAs (P = 0.02) in comparison to the normal kidney. Pathway analysis using global miRNA (n=12) and chromosomal Copy number variations (n=21) revealed a common developmental theme between PA and the PRCCs. Whole exome next-generation sequencing (n=12) showed a KMT2C specific pathogenic mutation among all PAs and PRCCs. KMT2C is a Chr 7 epigenetic regulator implicated in development and oncogenesis. Collectively results show a possible connection of PRCCs to PA and progenitor-like cell population, w...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research