) Eighty percent of germ cell tumors (GCT) have an i(12p), and the remaining 20 percent have over-representation of sequences derived from chromosome arm 12p elsewhere in the genome. This suggests that there is a gene(s) on chromosome arm 12p that is amplified and promotes oncogenesis in all GCT. We hypothesize that there is a 12p """"""""minimal amplified region"""""""" (MAR) in all adult GCT and that over-representation and subsequent overexpression of a gene(s) in the MAR contribute to tumorigenesis in GCT. This research will identify the MAR and the gene(s) within it that are necessary for the development of GCT. We will gradually narrow the known amplified regions of 12p by the study of GCT with 12p amplified regions in derivative chromosomes, using fluorescence in situ hybridization (FISH) and progressively smaller probes, and comparative genome hybridization (CGH). We will then identify candidate cDNA/genes in the MAR using cDNA selection and searching genome databases. Expression of candidate cDNAs and genes will be analyzed primarily by northern blotting. Another aim of this research is to identify genetic alterations that contribute to non-cure vs. cure of GCT. Copy number of chromosome arm 12p and of the MAR will be compared in tumors from non-cured or cured GCT. The results of our study of non-cured (relapsed/refractory) vs. cured tumors will be correlated with the results of other investigations of this program project.
