This study proposes to characterize genetic alterations in human borderline ovarian tumors. DNA extracted from fresh as well as paraffin embedded tumor tissues and the corresponding normal tissues will be used. Specific probes for detection of human DNA polymorphism including restriction fragment length polymorphism (RFLP), variable number of tandem repeats (VNTR) and microsatellite DNA, will be used to define the pattern of loss of heterozygosity in borderline ovarian tumors. Specific PCR primers will be used to amplify regions of tumor suppressor genes and proto-oncogenes and examined for mutation using single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing methods. Furthermore, a new approach called arbitrarily primed PCR (AP-PCR) will also be adapted to identify genetic changes in the borderline ovarian tumors. DNA fingerprints generated by arbitrarily designed primers from the tumor tissues will be compared with that from their corresponding normal counterparts. Alterations identified by this method together with those identified by LOH study will be used to compare with that of frankly invasive carcinomas in order to define the prognostic markers for borderline ovarian tumors. Borderline ovarian tumors, by definition, do not invade the stroma at the ovary. However, intraperitoneal tumor metastasis outside the pelvis are present in about 14 % of these tumors. The peritoneal tumors may represent true tumor implants disseminated from the primary tumor or may be tumors independently developed from the peritoneum. Molecular genetic techniques are now available to determine if these tumors are developed from the same tumor clone (a unifocal origin) or are independently developed primary tumors (multifocal origin). These techniques include X-chromosome methylation, loss of heterozygosity, specific point mutation and DNA fingerprinting. Some of the peritoneal tumor implants in borderline ovarian tumors display invasive histological features distinct from the non- invasive appearance of the primary tumors. The existence of two biologically distinct forms of tumor with different invasive properties within the same patient may provide unique opportunity to characterize the genetic changes underlying the mechanism of tumor invasion. Borderline ovarian tumors appear to fall in a histopathological continuum between benign tissues and invasive disease. By characterizing genetic changes in this possible precursor lesion, insights into the early genetic events involved in the pathogenesis of ovarian tumors may be obtained. Genetic markers may also be identified which may be useful for prediction of clinical behavior of borderline ovarian tumors and may affect the choice of treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA063381-02
Application #
2105186
Study Section
Pathology B Study Section (PTHB)
Project Start
1994-05-10
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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