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Open Access Highly Accessed Research article

Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa

Stefan Enroth15, Alvaro Rada-Iglesisas126, Robin Andersson17, Ola Wallerman2, Alkwin Wanders2, Lars Påhlman3, Jan Komorowski14 and Claes Wadelius2*

Author Affiliations

1 The Linnaeus Centre for Bioinformatics, Department of Cell and Molecular Biology, Science for Life Laboratory, Biomedical Center, Uppsala University, Box 598, SE-75124 Uppsala, Sweden

2 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden

3 Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden

4 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, PL-02-106 Warszawa, Poland

5 Current address: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden

6 Current address: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA

7 Current address: Department of Biology, Bioinformatics Centre, University of Copenhagen, Ole Maaloes Vej 5 DK-2200, Copenhagen N, Denmark

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BMC Cancer 2011, 11:450  doi:10.1186/1471-2407-11-450

Published: 19 October 2011

Abstract

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.