Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes

Publication date: 8 August 2017
Source:Cell Reports, Volume 20, Issue 6
Author(s): David Lindgren, Pontus Eriksson, Krzysztof Krawczyk, Helén Nilsson, Jennifer Hansson, Srinivas Veerla, Jonas Sjölund, Mattias Höglund, Martin E. Johansson, Håkan Axelson
Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts.

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Teaser

The kidney is a highly complex organ composed of many different cell types. Lindgren et al. find that cell-type-specific gene signatures can be extracted from normal kidney tissue samples. Here, these gene signatures are used to define the cellular origin of kidney cancers.


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