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

Lindgren, David LU ; Eriksson, Pontus LU ; Krawczyk, Krzysztof LU ; Nilsson, Helén LU ; Hansson, Jennifer LU ; Veerla, Srinivas LU ; Sjölund, Jonas LU ; Höglund, Mattias LU ; Johansson, Martin E. LU and Axelson, Håkan LU (2017) In Cell Reports 20(6). p.1476-1489
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell of origin, FOXI1, gene expression, HIF, kidney, nephron, NHF, RCC, renal cell carcinoma
in
Cell Reports
volume
20
issue
6
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:85026887625
  • wos:000407130400020
ISSN
2211-1247
DOI
10.1016/j.celrep.2017.07.043
language
English
LU publication?
yes
id
ea08fb53-b4b9-4b70-9bc0-cb80b61b5c17
date added to LUP
2017-08-29 13:35:16
date last changed
2017-09-18 11:43:21
@article{ea08fb53-b4b9-4b70-9bc0-cb80b61b5c17,
  abstract     = {<p>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.</p>},
  author       = {Lindgren, David and Eriksson, Pontus and Krawczyk, Krzysztof and Nilsson, Helén and Hansson, Jennifer and Veerla, Srinivas and Sjölund, Jonas and Höglund, Mattias and Johansson, Martin E. and Axelson, Håkan},
  issn         = {2211-1247},
  keyword      = {cell of origin,FOXI1,gene expression,HIF,kidney,nephron,NHF,RCC,renal cell carcinoma},
  language     = {eng},
  month        = {08},
  number       = {6},
  pages        = {1476--1489},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes},
  url          = {http://dx.doi.org/10.1016/j.celrep.2017.07.043},
  volume       = {20},
  year         = {2017},
}