Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase...

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Vydané v:	Journal of clinical oncology Ročník 23; číslo 27; s. 6569
Hlavní autori:	Hoque, Mohammad Obaidul, Topaloglu, Ozlem, Begum, Shahnaz, Henrique, Rui, Rosenbaum, Eli, Van Criekinge, Wim, Westra, William H, Sidransky, David
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 20.09.2005
Predmet:	Adult Aged Aged, 80 and over Biomarkers, Tumor - urine Case-Control Studies DNA Methylation DNA, Neoplasm - genetics DNA, Neoplasm - urine Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor - physiology Humans Logistic Models Male Middle Aged Neoplasm Proteins - urine Polymerase Chain Reaction - methods Probability Promoter Regions, Genetic Prostatic Neoplasms - genetics Prostatic Neoplasms - surgery Prostatic Neoplasms - urine Reference Values Sensitivity and Specificity Urinalysis
ISSN:	0732-183X
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Abstract	Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.
AbstractList	Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA.PURPOSEAberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA.We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls.PATIENTS AND METHODSWe tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls.Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels.RESULTSPromoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels.Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.CONCLUSIONOverall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer. Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.
Author	Rosenbaum, Eli Westra, William H Van Criekinge, Wim Henrique, Rui Hoque, Mohammad Obaidul Topaloglu, Ozlem Sidransky, David Begum, Shahnaz
Author_xml	– sequence: 1 givenname: Mohammad Obaidul surname: Hoque fullname: Hoque, Mohammad Obaidul organization: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA – sequence: 2 givenname: Ozlem surname: Topaloglu fullname: Topaloglu, Ozlem – sequence: 3 givenname: Shahnaz surname: Begum fullname: Begum, Shahnaz – sequence: 4 givenname: Rui surname: Henrique fullname: Henrique, Rui – sequence: 5 givenname: Eli surname: Rosenbaum fullname: Rosenbaum, Eli – sequence: 6 givenname: Wim surname: Van Criekinge fullname: Van Criekinge, Wim – sequence: 7 givenname: William H surname: Westra fullname: Westra, William H – sequence: 8 givenname: David surname: Sidransky fullname: Sidransky, David
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/16170165$$D View this record in MEDLINE/PubMed
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SubjectTerms	Adult Aged Aged, 80 and over Biomarkers, Tumor - urine Case-Control Studies DNA Methylation DNA, Neoplasm - genetics DNA, Neoplasm - urine Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor - physiology Humans Logistic Models Male Middle Aged Neoplasm Proteins - urine Polymerase Chain Reaction - methods Probability Promoter Regions, Genetic Prostatic Neoplasms - genetics Prostatic Neoplasms - surgery Prostatic Neoplasms - urine Reference Values Sensitivity and Specificity Urinalysis
Title	Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects
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