title: Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer.
abstract: BACKGROUND
  DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer.
  
  
  METHODS
  Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis.
  
  
  RESULTS
  We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma.
  
  
  CONCLUSIONS
  Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Jatin K
authors.initials: JK
authors.lastname: Nagpal
authors.forename: Carmen
authors.initials: C
authors.lastname: Jeronimo
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Ostrow
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Vim
authors.initials: V
authors.lastname: van Criekinge
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Chu-So
authors.initials: CS
authors.lastname: Moon
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D051929:CD146 Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011467:Prostate / Q000473:pathology / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C497902:MCAM protein, human