(Applicant's Description): Germ cell tumors (GCT), while uncommon, are still the leading cause of cancer in young adult males. Studies performed here at Indiana University have lead to therapeutic advances that now cure approximately eight out of ten patients with disseminated germ cell tumors. However, the remaining 20 percent have been intractable to therapy. Yet it is difficult to distinguish curable from incurable GCT at presentation with current clinically-based prognostic models. This question is probably the most important remaining issue in germ cell neoplasia. The central hypothesis driving this program is that there are molecular and cellular characteristics of high versus normal risk GCT. Defining these characteristics will certainly have diagnostic benefit, in that these patients could have aggressive therapy such as stem cell transplant offered prior to overwhelming disease or organ failure. In addition, it is possible that this group could have treatment studies defined for them, allowing the majority of germ cell patients to escape the increased toxicity that an aggressive regimen or surgery might bring. This program will attempt to define the molecular and cellular characteristics of high risk GCT in three projects. Project 1 will study the role that the novel transcriptional repressor Genesis has in GCT. Project 2 will isolate and characterize amplified GCT oncogenes on the marker chromosome iso12p. Project 3 will use PCR to analyze the significance of minimal residual circulating GCT cells. Core A will regulate sample distribution. Core B will collect the clinical data obtained from its own efforts, and scientific data from the other projects, and correlate it with clinical presentation and outcome of GCT. Core C will serve as the administrative center. The ultimate goal of this program is to define a prognostic model based on molecular and cellular characteristics that can distinguish high risk GCT. These distinguishing characteristics are potential targets for future therapy.
