To determine if novel specific oncogenes are associated with human neuroendocrine malignancies (apudomas), we are studying three of these tumor types with varying metastatic potential: insulinoma, medullary thyroid carcinoma, and choriocarcinoma. To detect the presence of more than one oncogene in each tumor, a sib selection step was added to the recently developed bioassay based on co-transfection of tumor DNA with a selectable marker gene (neo) followed by tumorigenesis testing in nude mice. Primary nude mouse tumors were obtained from each type of human apudoma. All primary tumor DNAs were tested for the presence of human alu repeat sequences and selected DNAs are currently undergoing a second round of transfection and tumorigenesis testing. Establishing the identity of oncogenes in these three tumor types will reveal if any common oncogenes operate in apudomas and if additional oncogenes are associated with metastatic potential. Further studies are underway to establish human pancreatic beta cell lines by transfection and microinjection of oncogenes. Growth factor supplemented serum free medium is also being used to stimulate long-term growth of primary islet cell cultures. Human pancreatic beta cell lines will be invaluable for assessing the immunological status of IDDM patients. Further studies on the mouse model of Reovirus type 1 induced polyendocrine disease have focused on the associated thyroiditis. In addition to the previously reported transient diabetes and growth retardation, infected mice develop mild thyroiditis characterized by focal destruction of acinar tissue, infiltration of inflammatory cells and the presence of autoantibodies to thyroglobulin and microsomal antigens. Thyroid involvement appears to be another manifestation of the generalized virus- induced polyendocrine disease.
