A Quantitative Promoter Methylation Profile of Prostate Cancer
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- Carmen Jerónimo
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of
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- Rui Henrique
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of
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- Mohammad O. Hoque
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of
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- Elizabeth Mambo
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of
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- Franclim R. Ribeiro
- 2Genetics,
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- Graça Varzim
- 2Genetics,
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- Jorge Oliveira
- 4Urology, Portuguese Oncology Institute-Porto, Porto, Portugal
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- Manuel R. Teixeira
- 2Genetics,
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- Carlos Lopes
- 3Pathology, and
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- David Sidransky
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of
Description
<jats:title>Abstract</jats:title> <jats:p>Purpose: Promoter hypermethylation is an alternative pathway for gene silencing in neoplastic cells and a promising cancer detection marker. Although quantitative methylation-specific PCR (QMSP) of the GSTP1 promoter has demonstrated near perfect specificity for cancer detection in prostate biopsies, we postulated that identification and characterization of additional methylation markers might further improve its high (80–90%) sensitivity.</jats:p> <jats:p>Experimental Design: We surveyed nine gene promoters (GSTP1, MGMT, p14/ARF, p16/CDKN2A, RASSF1A, APC, TIMP3, S100A2, and CRBP1) by QMSP in tissue DNA from 118 prostate carcinomas, 38 paired high-grade prostatic intraepithelial neoplasias (HGPIN), and 30 benign prostatic hyperplasias (BPH). The methylation levels were calculated and were correlated with clinical and pathologic indicators.</jats:p> <jats:p>Results: Only the methylation frequencies of GSTP1 and APC were significantly higher in prostate carcinoma compared with BPH (P < 0.001). Methylation levels of GSTP1, APC, RASSF1A, and CRBP1, differed significantly between prostate carcinoma and HGPIN, and/or HGPIN or BPH (P < 0.0001).With QMSP and empirically defined cutoff values, the combined use of GSTP1 and APC demonstrated a theoretical sensitivity of 98.3% for prostate carcinoma, with 100% specificity. Methylation levels were found to correlate with tumor grade (GSTP1 and APC) and stage (GSTP1, RASSF1A, and APC).</jats:p> <jats:p>Conclusions: Our data demonstrate the existence of a progressive increase of promoter methylation levels of several cancer-related genes in prostate carcinogenesis, providing additional markers to augment molecular detection of prostate carcinoma. Because methylation levels of GSTP1, APC, and RASSF1A are associated with advanced grade and stage, QMSP might augment the pathologic indicators currently used to predict tumor aggressiveness.</jats:p>
Journal
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- Clinical Cancer Research
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Clinical Cancer Research 10 (24), 8472-8478, 2004-12-15
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1363670318380020608
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- ISSN
- 15573265
- 10780432
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- Data Source
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- Crossref