Comprehensive molecular characterization of clear cell renal cell carcinoma
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 s...
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Nature Publishing Group
2018
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Online Access: | http://hdl.handle.net/1721.1/116727 |
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author | Getz, Gad Asher Voet, Douglas Lin, Pei Chin, Lynda Lander, Eric Steven |
author2 | Broad Institute of MIT and Harvard |
author_facet | Broad Institute of MIT and Harvard Getz, Gad Asher Voet, Douglas Lin, Pei Chin, Lynda Lander, Eric Steven |
author_sort | Getz, Gad Asher |
collection | MIT |
description | Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. |
first_indexed | 2024-09-23T11:32:06Z |
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id | mit-1721.1/116727 |
institution | Massachusetts Institute of Technology |
last_indexed | 2024-09-23T11:32:06Z |
publishDate | 2018 |
publisher | Nature Publishing Group |
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spelling | mit-1721.1/1167272022-09-27T20:11:17Z Comprehensive molecular characterization of clear cell renal cell carcinoma Getz, Gad Asher Voet, Douglas Lin, Pei Chin, Lynda Lander, Eric Steven Broad Institute of MIT and Harvard Massachusetts Institute of Technology. Department of Biology Getz, Gad Asher Voet, Douglas Lin, Pei Chin, Lynda Lander, Eric Steven Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. 2018-07-02T18:58:21Z 2018-07-02T18:58:21Z 2013-07 2012-10 2018-06-28T17:04:47Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/116727 Creighton, Chad J. et al. “Comprehensive Molecular Characterization of Clear Cell Renal Cell Carcinoma.” Nature 499, 7456 (June 2013): 43–49 © 2013 Macmillan Publishers Limited http://dx.doi.org/10.1038/NATURE12222 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group Nature |
spellingShingle | Getz, Gad Asher Voet, Douglas Lin, Pei Chin, Lynda Lander, Eric Steven Comprehensive molecular characterization of clear cell renal cell carcinoma |
title | Comprehensive molecular characterization of clear cell renal cell carcinoma |
title_full | Comprehensive molecular characterization of clear cell renal cell carcinoma |
title_fullStr | Comprehensive molecular characterization of clear cell renal cell carcinoma |
title_full_unstemmed | Comprehensive molecular characterization of clear cell renal cell carcinoma |
title_short | Comprehensive molecular characterization of clear cell renal cell carcinoma |
title_sort | comprehensive molecular characterization of clear cell renal cell carcinoma |
url | http://hdl.handle.net/1721.1/116727 |
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