The neoplastic potential of germ cells changes as they progress through normal development. This is reflected in correlations between the stage of origin, defined by genetic markers, and the morphology and natural history of resultant tumors. The determinants of this effect are unknown, and this tidy proposes to evaluate several possibilities in a collection of human germ cell tumors of defined origin. One is that cellular oncogenies, c-oncs, which are regulated in normal germ cells, are aberrantly expressed and/or mutated in the tumors. Gross cytogenetic anomalies will also be evaluated, as some abnormalities appear consistently in specific tumor types. Coincident with these human studies, parthenogenetic mouse ova will be used as a model system to directly study gene expression from the time of neoplastic transformation through proliferation into a teratoma. Using probes for genes regulated during normal gametogenesis and embryogenesis, including c-oncs, parthenogenetic embryo expression will be contrasted with normal embryos and mature teratomas from the same lineage. A particular effort will be made to determine if the patterns of c-onc expression present in the stem cell at the time of neoplastic transformation are altered during clonal proliferation of tumor cells.
