Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer

Hannah Flebbe, Feda H. Hamdan, Vijayalakshmi Kari, Julia Kitz, Jochen Gaedcke, B. Michael Ghadimi, Steven Johnsen, Marian Grade

Research output: Contribution to journalArticle

Abstract

Epigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell lines, only limited data are available from primary tumors. We therefore examined whether cancer-specific alterations in H3K27ac occupancy can be identified in primary rectal cancer. Tissue samples from primary rectal cancer and matched mucosa were obtained. ChIP-seq for H3K27ac was performed and differentially occupied regions were identified. The expression of selected genes displaying differential occupancy between tumor and mucosa were examined in gene expression data from an independent patient cohort. Differential expression of four proteins was further examined by immunohistochemistry. ChIP-seq for H3K27ac in primary rectal cancer and matched mucosa was successfully performed and revealed differential binding on 44 regions. This led to the identification of genes with increased H3K27ac, i.e., RIPK2, FOXQ1, KRT23, and EPHX4, which were also highly upregulated in primary rectal cancer in an independent dataset. The increased expression of these four proteins was confirmed by immunohistochemistry. This study demonstrates the feasibility of ChIP-seq-based epigenome mapping of primary rectal cancer and confirms the value of H3K27ac occupancy to predict gene expression differences.

Original languageEnglish (US)
Article number1142
JournalCancers
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Chromatin Immunoprecipitation
Rectal Neoplasms
Gene Expression
Mucous Membrane
Neoplasms
Immunohistochemistry
Feasibility Studies
Acetylation
Epigenomics
Histones
Genes
Lysine
Proteins
Cell Line

Keywords

  • ChIP-seq
  • Chromatin
  • Epigenetics
  • Gene expression
  • H3K27ac
  • Histone modification
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Flebbe, H., Hamdan, F. H., Kari, V., Kitz, J., Gaedcke, J., Ghadimi, B. M., ... Grade, M. (2019). Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer. Cancers, 11(8), [1142]. https://doi.org/10.3390/cancers11081142

Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer. / Flebbe, Hannah; Hamdan, Feda H.; Kari, Vijayalakshmi; Kitz, Julia; Gaedcke, Jochen; Ghadimi, B. Michael; Johnsen, Steven; Grade, Marian.

In: Cancers, Vol. 11, No. 8, 1142, 01.08.2019.

Research output: Contribution to journalArticle

Flebbe, H, Hamdan, FH, Kari, V, Kitz, J, Gaedcke, J, Ghadimi, BM, Johnsen, S & Grade, M 2019, 'Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer', Cancers, vol. 11, no. 8, 1142. https://doi.org/10.3390/cancers11081142
Flebbe H, Hamdan FH, Kari V, Kitz J, Gaedcke J, Ghadimi BM et al. Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer. Cancers. 2019 Aug 1;11(8). 1142. https://doi.org/10.3390/cancers11081142
Flebbe, Hannah ; Hamdan, Feda H. ; Kari, Vijayalakshmi ; Kitz, Julia ; Gaedcke, Jochen ; Ghadimi, B. Michael ; Johnsen, Steven ; Grade, Marian. / Epigenome mapping identifies tumor-specific gene expression in primary rectal cancer. In: Cancers. 2019 ; Vol. 11, No. 8.
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