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Tubular Progenitor Cells in End-Stage Kidney Disease and Papillary Adenomas

By: Anna Nowogrodzki
Posted: Monday, September 16, 2019

Samples of end-stage kidney disease and papillary adenoma contained kidney tubular progenitor cells, according to new study published in The American Journal of Pathology by George M. Yousef, MD, PhD, of the Hospital for Sick Children in Toronto, and colleagues. Possible evolution of papillary renal cell carcinoma from early preneoplastic lesions into different neoplastic subtypes was explored.

“Papillary adenoma could represent the link between end-stage kidney disease and papillary renal cell carcinoma,” the investigators commented. “Understanding initiation events that drive papillary renal cell carcinoma oncogenesis could potentially have a significant impact on papillary renal cell carcinoma prevention and management.”

The researchers performed immunohistochemistry on 140 samples from three Canadian medical centers: 108 papillary renal cell carcinomas, 20 papillary adenomas, 7 samples of end-stage kidney disease, and 5 samples of normal kidneys. They used markers that stain renal tubular progenitor cells and epithelial stem cells. They also performed whole-exome sequencing on 12 samples: 9 papillary renal cell carcinomas (3 samples each of 3 different subtypes) and 3 papillary adenomas.

There were significantly more renal tubular progenitor cells in the end-stage kidney disease samples and the papillary adenoma samples than in the normal kidneys. Whole-exome sequencing determined that all 12 samples, both papillary adenomas and papillary renal cell carcinomas, shared a particular pathogenic mutation in the gene KMT2C, a reported tumor suppressor that may be responsible for epigenetic changes.

Genetic analysis also found that each of the three subtypes of papillary renal cell carcinomas had its own distinct set of mutations, suggesting they are indeed distinct subtypes. However, one study limitation is the small number of samples (12) in the whole-exome sequencing analysis, so validation of these findings in additional studies is necessary.

Disclosure: The study authors reported no conflicts of interest.



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