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-...

Full description

Saved in:
Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2013-04, Vol.15 (4), p.399-IN13
Main Authors: Yang, Bing, Bhusari, Sachin, Kueck, Jessica, Weeratunga, Pushpa, Wagner, Jennifer, Leverson, Glen, Huang, Wei, Jarrard, David F
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Caveolin 1 - genetics
DNA Methylation
Epigenesis, Genetic
Fibroblast Growth Factor 1 - genetics
Gene Expression
Guanine Nucleotide Exchange Factors - genetics
Homeodomain Proteins - genetics
Humans
Male
Middle Aged
Molecular Diagnostic Techniques
Oncology
Prostate - metabolism
Prostate - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Rho Guanine Nucleotide Exchange Factors
Sequence Analysis, DNA
Transcriptome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.13280