Development and Validation of a FISH-Based Renal Cancer Detection Assay
Small Business Information
CANCER GENETICS, INC., 201Route 17 North, Rutherford, NJ, -
AbstractDESCRIPTION (provided by applicant): Increased routine use of state-of-the-art imaging techniques has resulted in a higher incidence of small incidentally discovered renal masses, benign and malignant. A large proportion of patients with such masses, are w ithin an older, more frail population and for renal cell carcinoma (RCC), 60-70% of patients now present asymptomatically. Treatment recommendations then with decreased morbidity are required for such patients, in a disease where current interventions incl ude minimally invasive to standard surgical procedures. Recently, the impact of morphology-based diagnosis of needle biopsies on treatment decision making has been identified to have two main limitations: inability to obtain diagnostic material of adequate quantity and quality for morphologic examination, and inability to distinguish particular RCC subtypes morphologically. In the current Phase I/Phase II application, we propose to develop a novel fluorescence in situ hybridization (FISH)-based renal cancer detection (FRCD) kit that is based not on cell morphology, but on the inherent differential genetics of renal cortical neoplasms, for commercial distribution by Cancer Genetics, Inc. Application of this test will permit diagnosis of the four predominant s ubtypes of renal cortical neoplasms (three malignant, one benign) that together with morphologic examination would impact all phases of clinical management of this disease. Phase I; Specific Aim 1: Retrospective validation of a BAC-based FISH probe panel i n discrimination of the four main subtypes of renal cortical neoplasms in renal core biopsies. Since preliminary studies using a BAC-based probe panel designed by CGI revealed good differential diagnosis of the four histologic subtypes, the sensitivity, sp ecificity, positive and negative predictive values of the probe panel will be validated in a cohort of 145 biopsies obtained from resected specimens with known but blinded morphology by standard pathology. Phase II; Specific Aim 1: Development of a single- copy FISH probe panel. In order to commercially distribute a FISH-based test without patent infringement of Cot-1 DNA use in hybridizations, a set of single-copy probes will be designed, propagated, labeled, and validated for use in a subset of renal needl e biopsies and surgical specimens used in Phase I. Phase II; Specific Aim 2: Prospective validation of the single-copy FISH probe panel as a potential assay in the diagnosis of RCC in needle biopsies. The panel of single-copy probes will be evaluated in im age-guided percutaneous renal biopsies prospectively obtained from patients with suspicious renal masses in an IRB-approved study. The accuracy of the assay will be evaluated with respect to the known but blinded morphology by standard pathology, of the 30 0 biopsies expected to be collected and assayed over two years. The overall goal of the project then is to develop, produce, and market a robust, sensitive, and specific FRCD kit that together with standard pathology will significantly contribute to clinic al decision making in patients with renal masses and kidney cancer, impacting patient treatment recommendations and cost of care. PUBLIC HEALTH RELEVANCE: With sophisticated imaging technologies routinely being used, kidney masses are often detected in old er patients, but it unclear if these masses are malignant and need treatment, or are benign. The genetic-based kidney cancer detection kit to be developed and validated in this application that can be used on needle biopsies of the mass obtained with few c omplications from such patients, will help clinicians and surgeons to make better treatment decisions and prevent needless costly surgical procedures.
* information listed above is at the time of submission.