CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction

A new prostate cancer biomarker

Wen Hsiang Lee, William B Isaacs, G. Steven Bova, William G Nelson

Research output: Contribution to journalArticle

Abstract

Cancer-associated somatic genome alterations offer great promise as cancer biomarkers. Here we describe a new biomarker for human prostate cancer: extensive methylation of deoxycytidine nucleotides distributed throughout a 5' 'CG island' region of the π-class glutathione S-transferase gene (GSTP1). Using the PCR to amplify a GSTP1 promoter sequence fragment containing 12 recognition sites for HpaII and MspI, 52 of 57 (91%) prostatic carcinoma DNA specimens demonstrated extensive somatic increases in deoxycytidine methylation, detected as amplification of target GSTP1 promoter sequences following HpaII digestion, but not following MspI treatment. Using nested primer sets, a sensitive PCR assay for extensive GSTP1 CG island methylation changes was developed that was capable of detecting 200 pg of prostate cancer cell DNA among 1 μg of normal leukocyte DNA. This GSTP1 CG island DNA methylation assay, which targets a somatic genome change present in most prostate cancer cells but not in normal cells, may serve as a new molecular diagnosis and staging tool to aid in prostate cancer detection and treatment.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume6
Issue number6
StatePublished - 1997

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Tumor Biomarkers
Islands
Methylation
Prostatic Neoplasms
Carcinoma
Polymerase Chain Reaction
Deoxycytidine
Genes
DNA
Genome
DNA Methylation
Glutathione Transferase
Digestion
Leukocytes
Nucleotides
Biomarkers
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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title = "CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: A new prostate cancer biomarker",
abstract = "Cancer-associated somatic genome alterations offer great promise as cancer biomarkers. Here we describe a new biomarker for human prostate cancer: extensive methylation of deoxycytidine nucleotides distributed throughout a 5' 'CG island' region of the π-class glutathione S-transferase gene (GSTP1). Using the PCR to amplify a GSTP1 promoter sequence fragment containing 12 recognition sites for HpaII and MspI, 52 of 57 (91{\%}) prostatic carcinoma DNA specimens demonstrated extensive somatic increases in deoxycytidine methylation, detected as amplification of target GSTP1 promoter sequences following HpaII digestion, but not following MspI treatment. Using nested primer sets, a sensitive PCR assay for extensive GSTP1 CG island methylation changes was developed that was capable of detecting 200 pg of prostate cancer cell DNA among 1 μg of normal leukocyte DNA. This GSTP1 CG island DNA methylation assay, which targets a somatic genome change present in most prostate cancer cells but not in normal cells, may serve as a new molecular diagnosis and staging tool to aid in prostate cancer detection and treatment.",
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AB - Cancer-associated somatic genome alterations offer great promise as cancer biomarkers. Here we describe a new biomarker for human prostate cancer: extensive methylation of deoxycytidine nucleotides distributed throughout a 5' 'CG island' region of the π-class glutathione S-transferase gene (GSTP1). Using the PCR to amplify a GSTP1 promoter sequence fragment containing 12 recognition sites for HpaII and MspI, 52 of 57 (91%) prostatic carcinoma DNA specimens demonstrated extensive somatic increases in deoxycytidine methylation, detected as amplification of target GSTP1 promoter sequences following HpaII digestion, but not following MspI treatment. Using nested primer sets, a sensitive PCR assay for extensive GSTP1 CG island methylation changes was developed that was capable of detecting 200 pg of prostate cancer cell DNA among 1 μg of normal leukocyte DNA. This GSTP1 CG island DNA methylation assay, which targets a somatic genome change present in most prostate cancer cells but not in normal cells, may serve as a new molecular diagnosis and staging tool to aid in prostate cancer detection and treatment.

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