IP Profile: Identification of Normal VS Potentially Precancerous Prostate Lesions
Our study with fifteen-Lipoxygenase type 1 (15-LO-1, ALOX15) gene suggests that we can distinguish precancerous lesions from benign lesions by assaying for a specific change in 15-LO-1 promoter DNA methylation status.
Organization: University of Pittsburgh
Inventors: Dr. Uddhav Kelavkar PhD, Dr. Rajiv Dhir MD, Dr. Denise O'Keefe PhD.
Industry Market: Pharma & Biotech
Technology Contact: Dr. Andrew Remes, PhD, Office of Enterprise Development, University of Pittsburgh
IP Update provided by A. Remes, U. Kelavkar, R. Dhir, and D. O’Keefe, University of Pittsburgh
Approximately half of the negative biopsies in men suspected to have prostate cancer clinically are "false negatives." The biggest hurdle is the inability to clearly distinguish the cancer precursor lesions from the benign prostatic intraepithelial neoplasia (PIN). When a lesion (considered "normal") has no cancer in a biopsy section at a given time, the patient is monitored continuously by repeated prostate biopsies and the treating physician is unable to recommend therapeutic options unless cancer is positively identified in a biopsy. This uncertainty tremendously affects an individual’s quality of life.
This has prompted the search for biomarkers or "malignancy associated changes" that may be identified on a "negative" biopsy that may indicate a high risk for the presence of cancer elsewhere in the gland. PIN and/or "normal appearing" epithelial cells (field-effect) have been identified as potential testable target tissues. In particular, "Normal appearing" and/or high grade prostatic intraepithelial neoplasia (HGPIN) are dangerous lesions and that it should be aggressively managed. Treatment of these precancerous lesions would be of clinical benefit notwithstanding the potential for cancer prevention.
Dr. Uddhav Kelavkar and colleagues at the University of Pittsburgh are able to distinguish truly normal (donor) tissues from cancer tissues, normal appearing adjacent normal tissue and/or cancer precursor PIN from benign PIN by assaying for a specific change in 15-LO-1 promoter DNA methylation status. To determine 15-LO-1 promoter methylation status, the inventors assessed 43 microdissected primary PCa specimens, 37 corresponding adjacent normal sections, 10 adjacent HG-PIN sections and 5 normal donor prostates. There was a statistically significant difference in methylation of 15-LO-1 CpG 10 from donors (truly normal) when compared with either "normal appearing", PIN or cancer samples.
A United States Non-Provisional Patent Application was published in Feb 2008 (20080044832). This invention allows for development of methods and kits of diagnosing or determining the prognosis of a cancer comprising determining the methylation status of the (15)-Lipoxygenase type 1 (15-LO-1) promoter in the tissue.
Reference: Publication: Kelavkar et al., DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation. Prostoglandins Other Lipid Mediat., 207 (Jan); 82 (1-4); 185-97.