The accumulation of genetic and epigenetic alterations at the sites of tumor suppressor genes and oncogenes has been associated with the progression of human malignancies. The long term goal of this application is the identification of a tumor suppressor gene(s) involved in the early stages of ovarian tumor development. The study of molecular genetic changes in ovarian cancer has been limited by the fact that tumor progression in this malignancy is not well understood. In particular, it is unclear whether a benign tumor or a low malignant potential tumor of the ovary can give rise to tumors of greater malignant potential. Nonetheless, studies of ovarian tumors have implicated at least 3 genes on chromosome 17 in the development of ovarian cancer. The proposed study will test the hypothesis that genetic alterations at 17pl3.3 are associated with low grade tumors and that genetic changes at 17q2l and at the p53 locus (17p13.1) are associated with high grade tumors. Particular attention will be focused on the study of low malignant potential lesions with the retrospective evaluation of allelic deletions in paraffin embedded ovarian tumors of low grade. Moreover, to determine if the accumulation of genetic alterations is correlated with the acquisition of a more malignant cellular phenotype, studies will also be performed at the different histologic areas within the same ovarian tumor. These studies will involve Southern and PCR methodologies. Eventually, chromosomal walking studies will be used to localize the tumor suppressor gene sequence on 17p13.3.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA060647-02
Application #
2101390
Study Section
Special Emphasis Panel (SRC (50))
Project Start
1993-08-01
Project End
1997-05-31
Budget Start
1994-08-01
Budget End
1995-05-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Pathology
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Pieretti, Maura; Hopenhayn-Rich, Claudia; Khattar, Nada H et al. (2002) Heterogeneity of ovarian cancer: relationships among histological group, stage of disease, tumor markers, patient characteristics, and survival. Cancer Invest 20:11-23
Tritz, D; Pieretti, M; Turner, S et al. (1997) Loss of heterozygosity in usual and special variant carcinomas of the endometrium. Hum Pathol 28:607-12
Pieretti, M; Turker, M S (1997) Mutation, ageing, and ovarian cancer. Lancet 349:700-1
Pieretti, M; Cavalieri, C; Conway, P S et al. (1995) Genetic alterations distinguish different types of ovarian tumors. Int J Cancer 64:434-40
Pieretti, M; Powell, D E; Gallion, H H et al. (1995) Genetic alterations on chromosome 17 distinguish different types of epithelial ovarian tumors. Hum Pathol 26:393-7
Pieretti, M; Powell, D E; Gallion, H H et al. (1995) Hypermethylation at a chromosome 17 ""hot spot"" is a common event in ovarian cancer. Hum Pathol 26:398-401
Shenson, D L; Gallion, H H; Powell, D E et al. (1995) Loss of heterozygosity and genomic instability in synchronous endometrioid tumors of the ovary and endometrium. Cancer 76:650-7