Methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer

Neoplasia. 2013 Apr;15(4):399-408. doi: 10.1593/neo.13280.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Rho Guanine Nucleotide Exchange Factors
  • Sequence Analysis, DNA
  • Transcriptome

Substances

  • CAV1 protein, human
  • Caveolin 1
  • Guanine Nucleotide Exchange Factors
  • Homeodomain Proteins
  • MCF2L protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • Fibroblast Growth Factor 1
  • EVX1 protein, human