Joint Fellowship Training Program
Mentor:
Rosalie K. Elespuru, PhD
Position and Organizational Affiliation:
Principle Investigator, Genomics & Genetics Lab, OSEL, Division of Biology, CDRH
Contact Information (email/phone):
rosalie.elespuru@fda.hhs.gov/301-796-0237
Running Title of Program:
Genetic Alterations and Cancer Risk
Research Project Summary:
Genetic alterations are implicated in the causation of cancer and recently have been used as biomarkers for diagnosis of cancer, stratification of patients into treatment groups, and monitors of therapy outcome. In the area of safety assessment (cancer prevention), we assess the capability for DNA interactions of new drugs, device materials, and food additives. In the area of cancer diagnosis and therapy, CDRH regulates genetic and genomic diagnostic devices, expected to be developed for the advent of "personalized medicine". Early diagnosis is a central goal in the prevention of metastatic tumor development. In both aspects a central theme is the analytical capability for detection of rare mutant DNA within a background of normal DNA sequences.
Proposed Project for IOTF Fellow:
Detection of mutant cancer biomarkers in blood. K-RAS codon 12 mutations are a common biomarker for lung and pancreas cancers, and the mutant DNA is shed into blood. DNA-based biomarkers can be used for diagnosis and the evaluation of therapy and relapse; however, there is considerable controversy over their utility. This project focuses on the development and testing of a mutant K-RAS-based diagnostic test for pancreas cancer, a cancer for which there are no available diagnostic tests and 95% fatalities within 6 months of diagnosis. We would experiment with allele-specific blocker PCR detection of mutant K-RAS (1), determining the levels of detection of the biomarker in surrogate blood and potentially in blood from cancer subjects. In addition, this project would define the technical issues relevant to robust detection of K-RAS mutant DNA in blood, relevant to review standards for genetic tests. With collaborators in the lab we have the capability to adapt the detection system to a “lab on a chip” for “point of care”, cancer diagnostics.
Regulatory Activity:
The fellow would have the opportunity to learn about the application of genetic analyses to cancer risk assessment of regulated products, including standards for genotoxicity testing, and issues involved in the risk/benefit assessment of products testing positive for genetic interactions. This would involve the Office of Device Evaluation as well as the FDA GeneTox Network. The second regulatory aspect involves genetic testing as used in diagnostic tests and personalized medicine. If this were chosen, the Fellow would become familiar with the development of new approaches to the regulation of genetic and genomic diagnostic microarray devices. This would involve geneticists, physicians and other scientists in the Office of In Vitro Diagnostics.
1. McKinzie PB, Parsons BL. (2002) Detection of rare K-ras codon 12 mutations using allele-specific competitive blocker PCR. Mutat Res. 517:209-20.
