An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer.
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.
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. amundadottirl@mail.nih.gov.
Jinping
J
Jia
Hemang
H
Parikh
Wenming
W
Xiao
Jason W
JW
Hoskins
Holger
H
Pflicke
Xuelu
X
Liu
Irene
I
Collins
Weiyin
W
Zhou
Zhaoming
Z
Wang
John
J
Powell
Snorri S
SS
Thorgeirsson
Udo
U
Rudloff
Gloria M
GM
Petersen
Laufey T
LT
Amundadottir
D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D045744:Cell Line, Tumor; D057890:Epigenomics; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA
D035683:MicroRNAs; D012333:RNA, Messenger; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)