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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Stefan Enroth, Alvaro Rada-Iglesisas, Robin Andersson, Ola Wallerman, Alkwin Wanders, Lars Påhlman, Jan Komorowski, Claes Wadelius

Published in: BMC Cancer | Issue 1/2011

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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.
Appendix
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Metadata
Title
Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa
Authors
Stefan Enroth
Alvaro Rada-Iglesisas
Robin Andersson
Ola Wallerman
Alkwin Wanders
Lars Påhlman
Jan Komorowski
Claes Wadelius
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-450

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