Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes
| Autor: | Krzysztof M. Krawczyk, Håkan Axelson, Pontus Eriksson, Srinivas Veerla, Jonas Sjölund, David Lindgren, Mattias Höglund, Helén Nilsson, Jennifer Hansson, Martin Johansson |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
kidney renal cell carcinoma medicine.medical_specialty NHF Chromophobe cell Nephron Biology urologic and male genital diseases General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Renal cell carcinoma Internal medicine medicine HIF Humans lcsh:QH301-705.5 Gene Carcinoma Renal Cell Kidney FOXI1 Forkhead Transcription Factors Nephrons cell of origin medicine.disease nephron RCC Kidney Neoplasms Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Endocrinology lcsh:Biology (General) gene expression Cancer research Kidney cancer Clear cell |
| Zdroj: | Cell Reports, Vol 20, Iss 6, Pp 1476-1489 (2017) |
| ISSN: | 2211-1247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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