Detecting DNA Methylation of the BCL2 , CDKN2A and NID2 Genes in Urine Using a Nested Methylation Specific Polymerase Chain Reaction Assay to Predict Bladder Cancer

甲基化 CDKN2A 医学 聚合酶链反应 DNA甲基化 图书馆学 内科学 基因 癌症 生物 遗传学 计算机科学 基因表达
作者
Michael Scher,Michael Elbaum,Yakov Mogilevkin,David W. Hilbert,Jack H. Mydlo,Avner Sidi,Martin E. Adelson,Eli Mordechai,Jason P. Trama
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:188 (6): 2101-2107 被引量:36
标识
DOI:10.1016/j.juro.2012.08.015
摘要

No AccessJournal of UrologyAdult Urology1 Dec 2012Detecting DNA Methylation of the BCL2, CDKN2A and NID2 Genes in Urine Using a Nested Methylation Specific Polymerase Chain Reaction Assay to Predict Bladder Cancer Michael B. Scher, Michael B. Elbaum, Yakov Mogilevkin, David W. Hilbert, Jack H. Mydlo, A. Ami Sidi, Martin E. Adelson, Eli Mordechai, and Jason P. Trama Michael B. ScherMichael B. Scher Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , Michael B. ElbaumMichael B. Elbaum Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , Yakov MogilevkinYakov Mogilevkin Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , David W. HilbertDavid W. Hilbert Femeris Women's Health Research Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , Jack H. MydloJack H. Mydlo Department of Urology, Temple University, Philadelphia, Pennsylvania , A. Ami SidiA. Ami Sidi Department of Urology, The E. Wolfson Medical Center, Holon, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel , Martin E. AdelsonMartin E. Adelson Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , Eli MordechaiEli Mordechai Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey , and Jason P. TramaJason P. Trama Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey View All Author Informationhttps://doi.org/10.1016/j.juro.2012.08.015AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Detection of methylated DNA has been shown to be a good biomarker for bladder cancer. Bladder cancer has the highest recurrence rate of any cancer and, as such, patients are regularly monitored using invasive diagnostic techniques. As urine is easily attainable, bladder cancer is an optimal cancer to detect using DNA methylation. DNA methylation is highly specific in cancer detection. However, it is difficult to detect because of the limited amount of DNA present in the urine of patients with bladder cancer. Therefore, an improved, sensitive and noninvasive diagnostic test is needed. Materials and Methods: We developed a highly specific and sensitive nested methylation specific polymerase chain reaction assay to detect the presence of bladder cancer in small volumes of patient urine. The genes assayed for DNA methylation are BCL2, CDKN2A and NID2. The regions surrounding the DNA methylation sites were amplified in a methylation independent first round polymerase chain reaction and the amplification product from the first polymerase chain reaction was used in a real-time methylation specific polymerase chain reaction. Urine samples were collected from patients receiving treatment at Wolfson Medical Center in Holon, Israel. Results: In a pilot clinical study using patient urine samples we were able to differentiate bladder cancer from other urogenital malignancies and nonmalignant conditions with a sensitivity of 80.9% and a specificity of 86.4%. Conclusions: We developed a novel methylation specific polymerase chain reaction assay for the detection and monitoring of bladder cancer using DNA extracted from patient urine. The assay may also be combined with other diagnostic tests to improve accuracy. References 1 : Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin2011; 61: 212. Google Scholar 2 : A surveillance schedule for G1Ta bladder cancer allowing efficient use of check cystoscopy and safe discharge at 5 years based on a 25-year prospective database. J Urol2005; 173: 1108. Link, Google Scholar 3 : Adherence to surveillance among patients with superficial bladder cancer. J Natl Cancer Inst2003; 95: 588. Google Scholar 4 : Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation. Health Technol Assess2006; 10: iii. 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Cell Oncol2004; 26: 291. Google Scholar 20 : Nidogen-2: a new basement membrane protein with diverse binding properties. J Mol Biol1998; 282: 99. Google Scholar 21 : The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ2011; 18: 1414. Google Scholar 22 : The meaning of p16(ink4a) expression in tumors: functional significance, clinical associations and future developments. Cell Cycle2011; 10: 2497. Google Scholar 23 : Role of urinary NMP-22 combined with urine cytology in follow-up surveillance of recurring superficial bladder urothelial carcinoma. Anal Quant Cytol Histol2008; 30: 25. Google Scholar 24 : The follow-up of patients with non-muscle-invasive bladder cancer by urine cytology, abdominal ultrasound and urine CYFRA 21–1: a pilot study. Anticancer Res2009; 29: 4281. Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byvan Kessel K, Van Neste L, Lurkin I, Zwarthoff E and Van Criekinge W (2015) Evaluation of an Epigenetic Profile for the Detection of Bladder Cancer in Patients with HematuriaJournal of Urology, VOL. 195, NO. 3, (601-607), Online publication date: 1-Mar-2016.Steers W (2012) This Month in Adult UrologyJournal of Urology, VOL. 188, NO. 6, (2029-2030), Online publication date: 1-Dec-2012. Volume 188Issue 6December 2012Page: 2101-2107Supplementary Materials Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.KeywordsDNA methylationurinary bladder neoplasmspolymerase chain reactionMetrics Author Information Michael B. Scher Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Michael B. Elbaum Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Yakov Mogilevkin Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author David W. Hilbert Femeris Women's Health Research Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Jack H. Mydlo Department of Urology, Temple University, Philadelphia, Pennsylvania Financial interest and/or other relationship with MDL. More articles by this author A. Ami Sidi Department of Urology, The E. Wolfson Medical Center, Holon, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel Financial interest and/or other relationship with Genesis Biotechnology Group. More articles by this author Martin E. Adelson Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Eli Mordechai Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Jason P. Trama Oncoveda Tumor Biology Center, Medical Diagnostic Laboratories LLC, a Division of Genesis Biotechnology Group, Hamilton, New Jersey Financial interest and/or other relationship with MDL. More articles by this author Expand All Advertisement PDF downloadLoading ...
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