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

David Lindgren, Pontus Eriksson, Krzysztof Krawczyk, Helén Nilsson, Jennifer Hansson, Srinivas Veerla, Jonas Sjölund, Mattias Höglund, Martin E. Johansson, Håkan Axelson

Research output: Contribution to journalArticlepeer-review

47 Citations (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)1476-1489
Number of pages14
JournalCell Reports
Volume20
Issue number6
DOIs
Publication statusPublished - 2017 Aug 8

Subject classification (UKÄ)

  • Bioinformatics and Systems Biology

Keywords

  • cell of origin
  • FOXI1
  • gene expression
  • HIF
  • kidney
  • nephron
  • NHF
  • RCC
  • renal cell carcinoma

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