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

Author:
  • David Lindgren
  • Pontus Eriksson
  • Krzysztof Krawczyk
  • Helén Nilsson
  • Jennifer Hansson
  • Srinivas Veerla
  • Jonas Sjölund
  • Mattias Höglund
  • Martin E. Johansson
  • Håkan Axelson
Publishing year: 2017-08-08
Language: English
Pages: 1476-1489
Publication/Series: Cell Reports
Volume: 20
Issue: 6
Document type: Journal article
Publisher: Cell Press

Abstract english

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.

Keywords

  • Bioinformatics and Systems Biology
  • cell of origin
  • FOXI1
  • gene expression
  • HIF
  • kidney
  • nephron
  • NHF
  • RCC
  • renal cell carcinoma

Other

Published
  • Clinical pathology, Malmö
  • ISSN: 2211-1247
Håkan Axelson
E-mail: hakan.axelson [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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