The goals of this project include the analysis of alterations in oncogenes and tumor suppressor genes in human endometrial carcinoma. PCR amplification, Southern blotting, and Northern blotting procedures have been successfully employed to evaluate oncogene activation (particularly of the K-ras gene) and tumor suppressor gene inactivation (particularly of the DCC gene) in 12 human endometrial carcinoma cell lines. These studies will be extended to primary human tumor specimens, both fresh and archival paraffin-embedded specimens, as well as to fresh tissue from several premalignant endometrial conditions. Similar strategies will be employed to evaluate potential molecular genetic alterations in endometriosis, especially as they may relate to those changes found in endometrial carcinoma. Endometriosis is a non-malignant condition of aberrant endometrial tissue growth, affecting 10-15% of the premenopausal U.S. population. In addition, collaborative studies are underway, the goals of which are to map tumor suppressor gene alterations that are common to tumors arising in a familial breast-ovarian cancer syndrome. PCR amplification and Southern blotting procedures will also be employed to analyze loss of heterozygosity at restriction fragment length polymorphic loci in familial breast and ovarian carcinoma DNA. The DNA from fixed and paraffin-embedded tumors was successfully extracted and analyzed as a prelude to these studies.