SBIR-STTR Award

The goal of this research is to develop a fluorescence in situ hybridization (FISH) assay for the detection of the t(14;18)(q32;q21) chromosomal translocation encountered in approximately 60% of B-cell lymphomas. These tumors are treated by chemotherapy and bone marrow transplantation; however, many patients relapse and become refractory to treatment. Diagnosis and post-treatment follow-up are performed by karyotype, Southern blotting, or PCR each of which has limitations of specificity and/or sensitivity. Therefore, another precise, reliable, and easy method to detect tumor cells, especially in the post-treatment set up is needed. Such a method is FISH. Unfortunately, no clinically tested probes are available for the detection of t(14;18) by FISH. In this Phase I application, we propose to develop a novel approach to unambiguously identify translocation carrying nuclei in diagnostic and follow-up patient samples. PROPOSED COMMERCIAL APPLICATION: The proposed research will provide a FISH assay to detect the t(14;18)(q32;q21) chromosomal translocation encountered in the majority of B-cell non-Hodgkin's lymphomas for use in cancer cytogenetic reference laboratories.

Approximately 60 percent of B-cell lymphomas are characterized by the presence of the t(14;18) (q32;q21) chromosomal translocation. Diagnosis and post-treatment follow-up are currently performed by karyotype, Southern blotting, or PCR, which have problems with specificity and sensitivity. Fluorescence in situ hybridization (FISH) addresses these limitations; however, no clinically tested FISH probes are available for detecting the t(14; 18) translocation. Phase I research developed novel probes for interphase FISH analysis of the t(14; 18) translocation. Using both normal and tumor samples, high sensitivity and specificity of the probes were observed. Using tumor specimens from multiple tissue types, Phase II research will validate use of the probes for diagnosis. Phase II research will also validate their use for monitoring minimal residual disease. In Phase II research, the probes will also be optimized to reduce background hybridization signal