Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types

To identify the transcriptional regulatory changes that are most widespread in solid tumors, we performed a pan-cancer analysis using over 600 pairs of tumors and adjacent normal tissues profiled in The Cancer Genome Atlas (TCGA). Frequency of upregulation was calculated across mRNA expression level...

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Main Authors:	Gross, Andrew M., Kreisberg, Jason F., Ideker, Trey
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640835/

id	pubmed-4640835
recordtype	oai_dc
spelling	pubmed-46408352015-11-13 Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types Gross, Andrew M. Kreisberg, Jason F. Ideker, Trey Research Article To identify the transcriptional regulatory changes that are most widespread in solid tumors, we performed a pan-cancer analysis using over 600 pairs of tumors and adjacent normal tissues profiled in The Cancer Genome Atlas (TCGA). Frequency of upregulation was calculated across mRNA expression levels, microRNA expression levels and CpG methylation sites and is provided here as a resource. Frequent tumor-associated alterations were identified using a simple statistical approach. Many of the identified changes were consistent with the increased rate of cell division in cancer, such as the overexpression of cell cycle genes and hypermethylation of PRC2 binding sites. However, we also identified proliferation-independent alterations, which highlight novel pathways essential to tumor formation. Nearly all of the GABA receptors are frequently downregulated, with the gene encoding the delta subunit (GABRD) strongly upregulated as the notable exception. Metabolic genes are also frequently downregulated, particularly alcohol dehydrogenases and others consistent with the decreased role of oxidative phosphorylation in cancerous cells. Alterations in the composition of GABA receptors and metabolism may play a key role in the differentiation of cancer cells, independent of proliferation. Public Library of Science 2015-11-10 /pmc/articles/PMC4640835/ /pubmed/26555223 http://dx.doi.org/10.1371/journal.pone.0142618 Text en © 2015 Gross et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gross, Andrew M. Kreisberg, Jason F. Ideker, Trey
spellingShingle	Gross, Andrew M. Kreisberg, Jason F. Ideker, Trey Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
author_facet	Gross, Andrew M. Kreisberg, Jason F. Ideker, Trey
author_sort	Gross, Andrew M.
title	Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
title_short	Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
title_full	Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
title_fullStr	Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
title_full_unstemmed	Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types
title_sort	analysis of matched tumor and normal profiles reveals common transcriptional and epigenetic signals shared across cancer types
description	To identify the transcriptional regulatory changes that are most widespread in solid tumors, we performed a pan-cancer analysis using over 600 pairs of tumors and adjacent normal tissues profiled in The Cancer Genome Atlas (TCGA). Frequency of upregulation was calculated across mRNA expression levels, microRNA expression levels and CpG methylation sites and is provided here as a resource. Frequent tumor-associated alterations were identified using a simple statistical approach. Many of the identified changes were consistent with the increased rate of cell division in cancer, such as the overexpression of cell cycle genes and hypermethylation of PRC2 binding sites. However, we also identified proliferation-independent alterations, which highlight novel pathways essential to tumor formation. Nearly all of the GABA receptors are frequently downregulated, with the gene encoding the delta subunit (GABRD) strongly upregulated as the notable exception. Metabolic genes are also frequently downregulated, particularly alcohol dehydrogenases and others consistent with the decreased role of oxidative phosphorylation in cancerous cells. Alterations in the composition of GABA receptors and metabolism may play a key role in the differentiation of cancer cells, independent of proliferation.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640835/
_version_	1613499747467788288

Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types

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