Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease

Rakesh Singal, Larry Ferdinand, Isildinha Reis, James J. Schlesselman

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Promoter methylation plays an important role in the inactivation of tumor suppressor genes during tumorigenesis. We examined the methylation status of glutathione S-transferase Pi1 (GSTP1), retinoic acid receptor beta (RARB), CD44, E-cadherin (ECAD), RAS association domain family protein 1A (RASSF1A) and endothelin B receptor (EDNRB) genes in 81 prostate cancer and 42 benign prostatic hyperpasia specimens. Genomic DNA was isolated from archived formaldehyde-fixed and paraffin-embedded tissue blocks. Methylation-specific PCR (MSP) was carried out after bisulfite treatment of genomic DNA. Methylation frequencies in prostate cancer and benign prostatic hyperplasia were 72% and 5% for GSTP1, 40% and 0% for RARB, 72% and 38% for CD44, 61% and 14% for ECAD, 49% and 19% for RASSF1A and 72% and 62% for EDNRB, respectively. Methylation of GSTP1, RARB, CD44, ECAD and RASSF1A, but not of EDNRB was detected at a statistically higher frequency in prostate cancer than in the benign prostatic hypertrophy specimens. Methylation of RARB occurred more frequently in early onset (age <55 years) as compared to late onset disease (age >70 years) (odds ratio, 8.6; 95% CI, 1.4-51.4; P=0.02). Methylation of RARB also occurred more frequently in stage III as compared to stage II disease (odds ratio, 3.2; 95% CI, 1.1-8.8; P=0.03). A methylation index (MI) was calculated as the total number of genes methylated, excluding EDNRB. A trend toward higher MI was noted in stage III as compared to stage II disease, and in Gleason score 7 as compared to Gleason score 6 tumors. Our results suggest that the methylation of selected genes in prostate cancers correlates with clinicopathological features of poor prognosis.

Original languageEnglish
Pages (from-to)631-637
Number of pages7
JournalOncology Reports
Volume12
Issue number3
StatePublished - Sep 1 2004

Fingerprint

Methylation
Prostatic Neoplasms
Genes
Cadherins
Glutathione Transferase
Neoplasm Grading
Prostatic Hyperplasia
Odds Ratio
Endothelin B Receptors
DNA
Tumor Suppressor Genes
Age of Onset
Paraffin
Formaldehyde
Carcinogenesis
retinoic acid receptor beta
Polymerase Chain Reaction

Keywords

  • DNA methylation
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease. / Singal, Rakesh; Ferdinand, Larry; Reis, Isildinha; Schlesselman, James J.

In: Oncology Reports, Vol. 12, No. 3, 01.09.2004, p. 631-637.

Research output: Contribution to journalArticle

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abstract = "Promoter methylation plays an important role in the inactivation of tumor suppressor genes during tumorigenesis. We examined the methylation status of glutathione S-transferase Pi1 (GSTP1), retinoic acid receptor beta (RARB), CD44, E-cadherin (ECAD), RAS association domain family protein 1A (RASSF1A) and endothelin B receptor (EDNRB) genes in 81 prostate cancer and 42 benign prostatic hyperpasia specimens. Genomic DNA was isolated from archived formaldehyde-fixed and paraffin-embedded tissue blocks. Methylation-specific PCR (MSP) was carried out after bisulfite treatment of genomic DNA. Methylation frequencies in prostate cancer and benign prostatic hyperplasia were 72{\%} and 5{\%} for GSTP1, 40{\%} and 0{\%} for RARB, 72{\%} and 38{\%} for CD44, 61{\%} and 14{\%} for ECAD, 49{\%} and 19{\%} for RASSF1A and 72{\%} and 62{\%} for EDNRB, respectively. Methylation of GSTP1, RARB, CD44, ECAD and RASSF1A, but not of EDNRB was detected at a statistically higher frequency in prostate cancer than in the benign prostatic hypertrophy specimens. Methylation of RARB occurred more frequently in early onset (age <55 years) as compared to late onset disease (age >70 years) (odds ratio, 8.6; 95{\%} CI, 1.4-51.4; P=0.02). Methylation of RARB also occurred more frequently in stage III as compared to stage II disease (odds ratio, 3.2; 95{\%} CI, 1.1-8.8; P=0.03). A methylation index (MI) was calculated as the total number of genes methylated, excluding EDNRB. A trend toward higher MI was noted in stage III as compared to stage II disease, and in Gleason score 7 as compared to Gleason score 6 tumors. Our results suggest that the methylation of selected genes in prostate cancers correlates with clinicopathological features of poor prognosis.",
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