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Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2011 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, 450- p.Article in journal (Refereed) Published
Abstract [en]

Background: Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Methods: Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. Results: By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. Conclusions: Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers.

Place, publisher, year, edition, pages
2011. Vol. 11, 450- p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-164440DOI: 10.1186/1471-2407-11-450ISI: 000297045500001OAI: oai:DiVA.org:uu-164440DiVA: diva2:468490
Available from: 2011-12-21 Created: 2011-12-20 Last updated: 2017-12-08Bibliographically approved

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Enroth, StefanWallerman, OlaWanders, AlkwinPahlman, LarsKomorowski, JanWadelius, Claes
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Science for Life Laboratory, SciLifeLabThe Linnaeus Centre for BioinformaticsDepartment of Immunology, Genetics and PathologyMedical GeneticsMolecular and Morphological PathologyColorectal Surgery
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