C04609: Optimal Use of a Panel of Methylation Markers with GSTP1 Hypermethylation in the DiagnosisValue Proposition:
• Detection and diagnosis of bladder, renal, and prostate cancers with increased improvement over histology alone
• Method to detect the recurrence of cancer in a patient currently undergoing treatment or previously treated for bladder, renal, and prostate cancers
• Method of determining the stage and clinical aggressiveness of cancer
• Method of selecting a treatment for a subject diagnosed with bladder, renal, and prostate by determining the methylation of a promoter in a biological sample, where an altered level of promoter methylation relative to a reference indicates the prognosis of the subject.
Technical Details:
BACKGROUND
Cancers, including bladder, renal, and prostate cancers, are a significant cause of human morbidity and mortality. Bladder cancer is the fourth most common cancer in men and the eighth in women both in terms of incidence and mortality; renal cancer kills approximately 12,000 Americans every year, and 30,000 new cases of renal cancer are reported each year in the United States; and prostate cancer is clinically diagnosed in one of every 11 American men. In their earliest stages, bladder, renal, and prostate cancers are clinically silent. When and if clinical symptoms do develop, patient diagnosis typically involves invasive procedures that lack sensitivity and accuracy. Highly reliable, noninvasive screening methods would permit patient screening, diagnosis, and prognostic evaluation. In addition, such methods would be useful for monitoring patients during or after cancer therapy.
TECHNOLOGY
JHU investigators have incorporated the use of Quantitative Methylation Specific PCR to quantitate the methylation status of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor beta2 (RARbeta2), and glutathione S-transferase pi (GSTP1) in order to increase the diagnostic accuracy of prostate biopsy histological examinations. Specifically, in a small study, histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARbeta2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone. The use of a panel of methylation markers as an adjunct to histological review may substantially augment prostate cancer diagnosis from needle biopsies (Tokumaru 2004).
Looking for Partners:
Commercial applications include a molecular test to improve diagnostic accuracy in prostate biopsies suspicious of cancer.
Publications/Associated Cases:
Tokumaru, Y., Harden, S. V., Sun, D. -., Yamashita, K., Epsiein, J. I., & Sidransky, D. (2004). Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma. Clinical Cancer Research, 10(16), 5518-5522.
