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

Research output: Contribution to journalArticle

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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Bioinformatics and Systems Biology

Keywords

  • cell of origin, FOXI1, gene expression, HIF, kidney, nephron, NHF, RCC, renal cell carcinoma
Original languageEnglish
Pages (from-to)1476-1489
Number of pages14
JournalCell Reports
Volume20
Issue number6
Publication statusPublished - 2017 Aug 8
Publication categoryResearch
Peer-reviewedYes