) This core is intended to be a resource for the SPORE as a whole and a valuable source of biological materials and genetic information for our continuing studies of the etiology of ovarian cancer. The Genetic Susceptibility Testing Laboratory Core will be responsible for the processing of blood samples collected through the """"""""Ovarian Cancer Clinical Network"""""""" Core directed by Dr. M. Daly. Biological samples collected at all participating sites will be forwarded to the Clinical Molecular Genetics Laboratory at the FCCC for processing and banking under CELIA approved guidelines. It is anticipated that approximately 4,300 peripheral blood samples will be collected and processed during the course of the proposed studies. These samples will come from women diagnosed with ovarian cancer and their first- and second-degree female relatives. A subset of these samples will be from breast cancer and breast/ovarian cancer syndrome families and will be tested for Geraldine mutations in BRCA1. As part of Project 4- """"""""Chemoprevention Studies in Patients at Risk for Ovarian Cancer"""""""", headed by Dr. Paul Engstrom, eligible participants will be enrolled onto clinical chemoprevention trials. The Genetic Susceptibility Testing Laboratory Core will also be responsible for the distribution of constitutional DNA samples from ovarian cancer patients to SPORE participants. Ovarian tumor DNA and corresponding normal (from peripheral blood) will be evaluated by Dr. Hamilton for loss of heterozygosity on chromosome q. and for mutational analysis of LOT. Blood samples will also be used in the several pilot studies. Dr. Raftogianis' project will require fresh blood specimens from ovarian cancer patients and from age matched controls for evaluation of arylsulfatase C (ARSC) activity and the presence of DNA polymorphisms within the human ARSC gene. Dr. Broccoli's project will require DNAs isolated from BRCA1 mutant allele carriers and age matched controls to establish if telomere length is a reliable marker for susceptibility to breast and/or ovarian cancer. Both Dr. Godwin (Project 2) and Dr. Broccoli (Pilot Project 1) will require fresh-frozen ovarian tumor tissue from BRCA1 mutation carriers. Dr. Godwin will use these samples to determine if the pattern of gene expression differs between sporadic and hereditary forms of ovarian cancer and Dr. Broccoli will determine the telomere dynamics in BRCA1-associated ovarian tumors. Overall, this proposal is a natural extension of our long term interest in the etiology of ovarian cancer and our Clinical Molecular Genetics laboratory will serve as the Genetic Susceptibility Testing Laboratory Core for the collection, processing, storage, and distribution of a large number of highly valuable bio-specimens, and for the BRCA1 mutation testing of women participating in chemoprevention trials.
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