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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hoque
Mohammad Obaidul
MO
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Topaloglu
Ozlem
O
Begum
Shahnaz
S
Henrique
Rui
R
Rosenbaum
Eli
E
Van Criekinge
Wim
W
Westra
William H
WH
Sidransky
David
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000652:urine*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000652:urine; D016133:Polymerase Chain Reaction / Q000379:methods; D011336:Probability; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000601:surgery / Q000652:urine*; D012016:Reference Values; D012680:Sensitivity and Specificity; D016482:Urinalysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins