C05150: Identification of Pathological BRCA2 Alleles and Variant-Specific Drug ScreeningNovelty:
A functional assay to identify genetic variants of tumor suppressor genes that may be associated with cancer risk, applicable for personalized therapy and genome-specific drug screening.
Value Proposition:
The formation of human cancers is often associated with genomic variants that cause loss-of-function mutations in tumor suppressor genes. Hence, methods to evaluate the significance of specific sequence variations will greatly help to predict cancer risk and enable clinicians to provide appropriate genetic counseling and personalized therapy. This invention is a novel approach to determine the relative risk due to specific individual mutations. Advantages of this invention include:
• Easy discrimination of benign and deleterious mutations
• Enables pharmaceutical companies to screen for novel compounds or conduct clinical trials of anticancer therapy
• Improves clinical utility of genetic tests of genetic testing companies and academic research on familial cancers
• Ethically acceptable technique to compare effects of subtly altering human genomes for personalized medicine
Technical Details:
Johns Hopkins researchers have established a new technique to evaluate the impact of specific allelic variations of medically critical genes on the formation of human disease by a simple homologous recombination technique producing syngeneic clones. The BRCA2 status of patients is commonly used to advise on cancer risk; however, many Variants of Unknown Significance (VUS) are uncharacterized with regard to their deleteriousness. This invention demonstrates a valuable new tool for the classification of genetic variations into harmful and benign mutations. A BRCA2 hemizygous mammalian cell line and a library of BRCA2 variants are provided, which enable to determine the deleteriousness of specific mutations based on the relative frequency of integration of BRCA2 variants at the intact or the already targeted allele. Moreover, null cells of medically critical genes, together with the various syngeneic clones can be used to screen for new drugs with high toxicity against specific pathogenic variants. Together, this presents a valuable new tool for individualized risk assessment of cancer and possibly any other human disease and the development of personalized medicine for efficient disease therapy.
Looking for Partners:
To develop and commercialize the technology as a new approach for the evaluation of the pathological significance of genomic variants and mutant-specific drug screening.
Stage of Development:
Pre-Clinical
Data Availability:
Under CDA / NDA
Publications/Associated Cases:
Cancer Biol Ther. 2007; 6(5):654-60.
Cancer Res 2008; 68:5023-30.
