Research Program Overview
The major focus in the laboratory is molecular oncology and the investigation of molecular genetic changes associated with women's cancers, both inherited and acquired. A subset of ovarian cancer patients is considered to have a hereditary predisposition. The BRCA1 and BRCA2 genes are implicated in the hereditary breast-ovarian cancer syndrome.. The primary approach has included surveys of somatic genetic alterations in tumors, and positional cloning and characterization of tumor suppressor and growth regulatory genes.
Hereditary Breast Cancer and Novel Hispanic BRCA Mutations
We are obtaining a comprehensive dataset on the prevalence and nature of BRCA mutations among Hispanics. We documented that the Jewish founder mutation, BRCA1 185delAG, is prevalent in Hispanic populations; we discovered a novel BRCA1 rearrangement, the result of an Alu repeat-mediated recombination event, that accounts for a substantial proportion of high-risk Hispanic families. We are developing and testing the clinical effectiveness of a panel of recurrent BRCA mutations on the Sequenom (mass spectroscopy) high throughput platform for prospective screening of high-risk clinic cohorts, supported in part by an NCI R03 grant (3/1/09) for the project. This will represent the largest series of Hispanics with BRCA mutation information and clinical annotation.
Markel Ovarian Cancer Research Program
This project has three main focuses: 1) The development of new tools and enhanced prediction models to identify women at increased risk of ovarian cancer in order to facilitate prevention and early detection; 2) Linking molecular diagnostics to molecular therapeutics to permit individualized therapy through enhanced recruitment infrastructure of clinical trials for BRCA carriers; 3) Examining outcomes of initial therapy for women with BRCA-associated ovarian cancer and looking for genotype/phenotype correlations that may shed light on mechanisms of acquired resistance to therapy.
Molecular Genetic Studies of Cancer Patients and Their Relatives
A key resource in the lab is our prospective hereditary cancer registry, which includes biospecimens (more than 7,000 samples to date) for investigating factors that may contribute to the development of specific cancers in cancer patients and/or their relatives. The registry includes one of the largest existing sets of BRCA1/2 carriers (>600 families) at a single institution. Data and biospecimens from the registry also enable participation in the multi-institutional consortia that are necessary to assemble enough hereditary cases for epidemiological studies. We demonstrated remarkable concordance for hormone collaborative receptor status in BRCA1/2 carriers with bilateral breast cancer (CEBP, 2005. 14: 1534-8). BRCA modifier gene studies are also being conducted.