title: Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma.
abstract: OBJECTIVE
  The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations.
  
  
  METHODS
  We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27,800 CpG islands covering 21 MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues and in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual.
  
  
  RESULTS
  This analysis identified 1,658 known loci that were commonly differentially methylated in pancreatic cancer compared with normal pancreas. By integrating the pancreatic DNA methylation status with the gene expression profiles of the same samples before and after treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, and the histone deacetylase inhibitor, trichostatin A, we identified dozens of aberrantly methylated and differentially expressed genes in pancreatic cancers including a more comprehensive list of hypermethylated and silenced genes that have not been previously described as targets for aberrant methylation in cancer.
  
  
  CONCLUSIONS
  We expected that the identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications.
authors: Department of Pathology, Oncology, and Medicine, Bloomberg School of Public Health, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Audrey
authors: A
authors: Vincent
authors: Noriyuki
authors: N
authors: Omura
authors: Seung-Mo
authors: SM
authors: Hong
authors: Andrew
authors: A
authors: Jaffe
authors: James
authors: J
authors: Eshleman
authors: Michael
authors: M
authors: Goggins
references: Gastroenterology. 2002 Jul;123(1):365-72
references: 12105864
references: J Natl Cancer Inst. 2003 Feb 19;95(4):327-30
references: 12591989
references: Cancer Biol Ther. 2008 Jul;7(7):1146-56
references: 18535405
references: Adv Surg. 2010;44:293-311
references: 20919528
references: Epigenetics. 2009 Nov 16;4(8):537-40
references: 19923920
references: Cancer Res. 2007 Nov 15;67(22):10899-909
references: 18006835
references: EMBO J. 2006 Jun 7;25(11):2326-37
references: 16724116
references: Int J Clin Exp Pathol. 2009;2(4):310-26
references: 19158989
references: Oncogene. 2005 Jan 27;24(5):850-8
references: 15592528
references: Genes Dev. 2006 Dec 1;20(23):3215-31
references: 17158741
references: Carcinogenesis. 2007 Jun;28(6):1178-87
references: 17227781
references: Oncogene. 2010 Apr 8;29(14):2104-17
references: 20154727
references: Science. 2008 Sep 26;321(5897):1801-6
references: 18772397
references: Cancer Res. 1997 Aug 1;57(15):3126-30
references: 9242437
references: Cancer Res. 2003 Jul 15;63(14):4158-66
references: 12874021
references: Cancer Res. 2010 Jan 15;70(2):543-51
references: 20068157
references: Cancer Res. 2006 Jan 15;66(2):1208-17
references: 16424060
references: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3919-24
references: 19237581
references: Clin Gastroenterol Hepatol. 2006 Jun;4(6):766-81; quiz 665
references: 16682259
references: BMC Cancer. 2008 May 30;8:154
references: 18513385
references: Mod Pathol. 2008 Dec;21(12):1499-507
references: 18820670
references: Diabetes. 2008 Mar;57(3):654-68
references: 18071024
references: Mol Cell Biol. 2007 Jul;27(13):4905-16
references: 17470549
references: Science. 2009 Apr 10;324(5924):217
references: 19264984
references: Br J Cancer. 2009 Jul 21;101(2):209-14
references: 19603030
references: Cancer Res. 2004 Feb 1;64(3):883-8
references: 14871816
references: Cancer Res. 2003 Jul 1;63(13):3735-42
references: 12839967
references: Clin Gastroenterol Hepatol. 2008 Nov;6(11):1270-8
references: 18995218
references: Gastroenterology. 2006 Feb;130(2):548-65
references: 16472607
references: Clin Cancer Res. 2008 Jan 1;14(1):55-61
references: 18172252
references: Epigenetics. 2009 Jul 1;4(5):307-312
references: 28001119
references: Cancer Res. 2000 Apr 1;60(7):1835-9
references: 10766168
references: Int J Cancer. 2009 Feb 15;124(4):827-33
references: 19035457
references: Cancer Res. 2010 Apr 1;70(7):2718-27
references: 20233874
references: Cancer Biol Ther. 2009 Nov;8(21):2013-24
references: 20037478
references: Cancer Res. 2006 Aug 15;66(16):7939-47
references: 16912168
references: EMBO J. 2007 Jul 25;26(14):3410-22
references: 17599062
references: Am J Pathol. 2002 May;160(5):1573-81
references: 12000709
references: Cancer Res. 2008 Apr 15;68(8):2745-54
references: 18417445
references: Cell. 2007 Feb 23;128(4):683-92
references: 17320506
references: Clin Cancer Res. 2003 Apr;9(4):1446-52
references: 12684418
references: J Biol Chem. 2009 Jan 30;284(5):2767-2777
references: 19028697
references: Mol Cancer Res. 2010 Jun;8(6):821-32
references: 20530583
references: Int J Cancer. 2010 Sep 1;127(6):1373-83
references: 20073063
references: Genome Res. 2007 Oct;17(10):1529-36
references: 17785535
references: Mol Oncol. 2009 Dec;3(5-6):425-38
references: 19497796
references: Clin Cancer Res. 2005 Jul 1;11(13):4681-8
references: 16000561
references: Genome Res. 2010 Oct;20(10):1369-82
references: 20716667
references: Clin Cancer Res. 2010 Mar 15;16(6):1781-9
references: 20215540