) 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA083638-01S1
Application #
6323322
Study Section
Special Emphasis Panel (ZCA1)
Project Start
1999-09-30
Project End
2000-09-29
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$47,602
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Nacson, Joseph; Krais, John J; Bernhardy, Andrea J et al. (2018) BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance. Cell Rep 25:1384
Gabbasov, Rashid; Xiao, Fang; Howe, Caitlin G et al. (2018) NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice. Oncogene 37:4854-4870
Chiang, Cheryl Lai-Lai; Kandalaft, Lana E (2018) In vivo cancer vaccination: Which dendritic cells to target and how? Cancer Treat Rev 71:88-101
Hu, Xiaowen; Sood, Anil K; Dang, Chi V et al. (2018) The role of long noncoding RNAs in cancer: the dark matter matters. Curr Opin Genet Dev 48:8-15
Nacson, Joseph; Krais, John J; Bernhardy, Andrea J et al. (2018) BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance. Cell Rep 24:3513-3527.e7
Beck, Tim N; Smith, Chad H; Flieder, Douglas B et al. (2017) Head and neck squamous cell carcinoma: Ambiguous human papillomavirus status, elevated p16, and deleted retinoblastoma 1. Head Neck 39:E34-E39
Yang, Lu; Zhang, Youyou; Shan, Weiwei et al. (2017) Repression of BET activity sensitizes homologous recombination-proficient cancers to PARP inhibition. Sci Transl Med 9:
Skates, Steven J; Greene, Mark H; Buys, Saundra S et al. (2017) Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials. Clin Cancer Res 23:3628-3637
Zhang, Dongmei; Zhang, Gao; Hu, Xiaowen et al. (2017) Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer. Cancer Res 77:3745-3757
Prudnikova, Tatiana Y; Chernoff, Jonathan (2017) The Group I Pak inhibitor Frax-1036 sensitizes 11q13-amplified ovarian cancer cells to the cytotoxic effects of Rottlerin. Small GTPases 8:193-198

Showing the most recent 10 out of 323 publications