Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes
(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.
(Less)
- author
- 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
- organization
- publishing date
- 2017-08-08
- 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
-
- pmid:28793269
- wos:000407130400020
- scopus:85026887625
- 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
- 2025-02-03 21:45:27
@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}}, keywords = {{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}}, doi = {{10.1016/j.celrep.2017.07.043}}, volume = {{20}}, year = {{2017}}, }