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 A.; Grade, Marian

doi:10.3390/cancers11081142

Open AccessArticle

Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer

by

Hannah Flebbe

^1,†,

Feda H. Hamdan

^1,2,†,

Vijayalakshmi Kari

^1,†,

Julia Kitz

³,

Jochen Gaedcke

¹,

B. Michael Ghadimi

¹,

Steven A. Johnsen

^1,2,*

and

Marian Grade

^1,*

¹

Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany

²

Gene Regulatory Mechanisms and Molecular Epigenetics Laboratory, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA

³

Institute of Pathology, University Medical Center Goettingen, 37075 Goettingen, Germany

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cancers 2019, 11(8), 1142; https://doi.org/10.3390/cancers11081142

Submission received: 28 June 2019 / Revised: 31 July 2019 / Accepted: 6 August 2019 / Published: 9 August 2019

(This article belongs to the Collection Histone Modification in Cancer)

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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.

Keywords: ChIP-seq; chromatin; epigenetics; histone modification; H3K27ac; rectal cancer; gene expression

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MDPI and ACS Style

Flebbe, H.; Hamdan, F.H.; Kari, V.; Kitz, J.; Gaedcke, J.; Ghadimi, B.M.; Johnsen, S.A.; Grade, M. Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer. Cancers 2019, 11, 1142. https://doi.org/10.3390/cancers11081142

AMA Style

Flebbe H, Hamdan FH, Kari V, Kitz J, Gaedcke J, Ghadimi BM, Johnsen SA, Grade M. Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer. Cancers. 2019; 11(8):1142. https://doi.org/10.3390/cancers11081142

Chicago/Turabian Style

Flebbe, Hannah, Feda H. Hamdan, Vijayalakshmi Kari, Julia Kitz, Jochen Gaedcke, B. Michael Ghadimi, Steven A. Johnsen, and Marian Grade. 2019. "Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer" Cancers 11, no. 8: 1142. https://doi.org/10.3390/cancers11081142

APA Style

Flebbe, H., Hamdan, F. H., Kari, V., Kitz, J., Gaedcke, J., Ghadimi, B. M., Johnsen, S. A., & Grade, M. (2019). Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer. Cancers, 11(8), 1142. https://doi.org/10.3390/cancers11081142

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Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer

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