DESCRIPTION: (Applicant's Description) Cancers of unknown primary site are a diagnostic and therapeutic dilemma in oncology. Information from DNA micro array technologies on the gene expression profile of cancers has led to the hypothesis that there are diagnostic sets of genes which can resolve the origin of unknown primary cancers (UPC) with a high degree of confidence. The purpose of this project is to test this hypothesis, by both retrospective and prospective analysis of cases of UPC from Stanford Medical Center and the Sarah Cannon Cancer Center, in the context of a rapidly evolving database of site-specific clusters of gene expression. Specific Aims are: (1) Definition of the gene expression profile of known human cancers. We now have extensive information on the profiles of lymphomas, leukemia, and carcinomas of the breast, prostate, lung, ovary, and liver. Additional tumors to be accrued from our tumor bank and ongoing sample acquisitions include sarcomas, germ cell cancers, melanomas, mesotheliomas, and carcinomas of the colon, stomach, pancreas, bladder, and kidney. (2) Determination of the diagnostic cluster of gene expression for each of the above tumor types. We anticipate that several hundred genes may differentiate one from the others of these known tumors. (3) Acquisition, gene expression profiling, and diagnostic classification of unknown primary cancer specimens. This aim will involve a close collaboration with the world's leading center for the clinical evaluation of unknown primary cancers, the Sarah Cannon Cancer Center in Nashville. (4) Evaluation of a panel of histospecific antisera for diagnostic utility with UPC specimens. This aim will utilize retrospective archived specimens as well as prospectively acquired samples from this project. (5) Identification of specific or clustered gene expression associated with known prognostic factors, response to therapies, and survival of patients with UPC.