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Open Access Highly Accessed Research article

An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer

Jinping Jia1, Hemang Parikh1, Wenming Xiao2, Jason W Hoskins1, Holger Pflicke3, Xuelu Liu24, Irene Collins1, Weiyin Zhou5, Zhaoming Wang5, John Powell2, Snorri S Thorgeirsson6, Udo Rudloff3, Gloria M Petersen7 and Laufey T Amundadottir1*

Author Affiliations

1 Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

2 Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bioinformatics and Molecular Analysis Section, Bethesda, MD 20892, USA

3 Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

4 SRA International, Fairfax, VA 22033, USA

5 Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

6 Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, MD 20892, USA

7 Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA

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BMC Medical Genomics 2013, 6:33  doi:10.1186/1755-8794-6-33

Published: 22 September 2013

Abstract

Background

Pancreatic cancer is a highly lethal cancer with limited diagnostic and therapeutic modalities.

Methods

To begin to explore the genomic landscape of pancreatic cancer, we used massively parallel sequencing to catalog and compare transcribed regions and potential regulatory elements in two human cell lines derived from normal and cancerous pancreas.

Results

By RNA-sequencing, we identified 2,146 differentially expressed genes in these cell lines that were enriched in cancer related pathways and biological processes that include cell adhesion, growth factor and receptor activity, signaling, transcription and differentiation. Our high throughput Chromatin immunoprecipitation (ChIP) sequence analysis furthermore identified over 100,000 regions enriched in epigenetic marks, showing either positive (H3K4me1, H3K4me3, RNA Pol II) or negative (H3K27me3) correlation with gene expression. Notably, an overall enrichment of RNA Pol II binding and depletion of H3K27me3 binding were seen in the cancer derived cell line as compared to the normal derived cell line. By selecting genes for further assessment based on this difference, we confirmed enhanced expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in two larger sets of pancreatic cancer cell lines and in tumor tissues as compared to normal derived tissues.

Conclusions

As aldehyde dehydrogenase (ALDH) activity is a key feature of cancer stem cells, our results indicate that a member of the ALDH superfamily, ALDH1A3, may be upregulated in pancreatic cancer, where it could mark pancreatic cancer stem cells.

Keywords:
Pancreatic cancer; Transcriptome; Epigenome; Sequencing; ALDH1A3