title: Methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer.
abstract: Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Sachin
authors.initials: S
authors.lastname: Bhusari
authors.forename: Jessica
authors.initials: J
authors.lastname: Kueck
authors.forename: Pushpa
authors.initials: P
authors.lastname: Weeratunga
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wagner
authors.forename: Glen
authors.initials: G
authors.lastname: Leverson
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: David F
authors.initials: DF
authors.lastname: Jarrard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051242:Caveolin 1 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D064067:Rho Guanine Nucleotide Exchange Factors; D017422:Sequence Analysis, DNA; D059467:Transcriptome
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; C577400:MCF2L protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; D016220:Fibroblast Growth Factor 1; C074437:EVX1 protein, human
references.citation: Cancer Control. 2010 Oct;17(4):245-55
references.pmid: 20861812
references.citation: J Pathol. 1999 Jan;187(1):61-81
references.pmid: 10341707
references.citation: Prostate. 2011 Nov;71(15):1621-30
references.pmid: 21432864
references.citation: Semin Cancer Biol. 2009 Jun;19(3):172-80
references.pmid: 19429481
references.citation: Cell Cycle. 2006 Jan;5(2):155-8
references.pmid: 16397413
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7
references.pmid: 16432200
references.citation: Oncogene. 2012 Nov 29;31(48):5029-37
references.pmid: 22310288
references.citation: J Urol. 1994 Nov;152(5 Pt 2):1709-13
references.pmid: 7933231
references.citation: Methods Enzymol. 2006;411:134-93
references.pmid: 16939790
references.citation: Nat Biotechnol. 2009 Apr;27(4):361-8
references.pmid: 19329998
references.citation: BMC Genomics. 2010 Feb 25;11:137
references.pmid: 20181289
references.citation: Science. 2005 Mar 25;307(5717):1976-8
references.pmid: 15731405
references.citation: Nat Genet. 2005 Aug;37(8):899-905
references.pmid: 16007089
references.citation: Nat Genet. 2005 Aug;37(8):853-62
references.pmid: 16007088
references.citation: Cancer Res. 2008 Aug 15;68(16):6797-802
references.pmid: 18701505
references.citation: Oncogene. 2011 Mar 24;30(12):1390-401
references.pmid: 21132003
references.citation: Mol Cancer Res. 2006 Jan;4(1):1-8
references.pmid: 16446401
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):255-61
references.pmid: 16478744
references.citation: Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R88-95
references.pmid: 17613553
references.citation: Nature. 1983 Jan 6;301(5895):89-92
references.pmid: 6185846
references.citation: Cancer Prev Res (Phila). 2012 Oct;5(10):1203-12
references.pmid: 22961779
references.citation: Cancer Res. 1998 Dec 15;58(24):5835-41
references.pmid: 9865743
references.citation: Arch Pathol Lab Med. 2007 Aug;131(8):1257-66
references.pmid: 17683188
references.citation: Cancer Res. 2010 Oct 15;70(20):8169-78
references.pmid: 20841482
references.citation: Urol Oncol. 2013 Jul;31(5):628-34
references.pmid: 21704537
references.citation: Biotechniques. 2006 Jun;40(6):721-2, 724, 726
references.pmid: 16774114
references.citation: Prostate. 2007 May 1;67(6):638-44
references.pmid: 17342751
references.citation: Science. 2003 Apr 18;300(5618):455
references.pmid: 12702868
references.citation: Cancer. 1953 Sep;6(5):963-8
references.pmid: 13094644
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Br J Cancer. 2009 Jan 27;100(2):240-5
references.pmid: 19002169
references.citation: Urology. 2011 Jan;77(1):249.e1-7
references.pmid: 21195844
references.citation: Oncogene. 2007 Jul 19;26(33):4761-73
references.pmid: 17325666
references.citation: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95
references.pmid: 16467114
references.citation: Adv Genet. 2010;71:3-39
references.pmid: 20933124
references.citation: Genes Dev. 2002 Jan 1;16(1):6-21
references.pmid: 11782440
references.citation: J Urol. 2013 Jun;189(6):2335-41
references.pmid: 23159584
references.citation: Cancer Res. 2003 Apr 15;63(8):1727-30
references.pmid: 12702551