LOSS OF HETEROZYGOSITY OF TUMOR-SUPPRESSOR GENES IN TESTIS CANCER

Little is known of the molecular changes that occur in germ cell tumor s (GCT) of the testis. We studied three GCT cell lines and 44 tumors f or loss of heterozygosity (LOH) of the tumor suppressor genes APC, MCC , DCC, RE, TP53, and WT-1. We observed that LOH occurred in 55% (21 of 38) of informative cases at DCC, in 28% (10 of 36) of informative cas es at APC,in 23% (6 of 26) at MCC, in 30% (13 of 43) at RB, and in 27% (6 of 22) at WT-1. The LOH level in these tumors using anonymous prim ers mapping to the short and long arms of chromosome 19, which is cyto genetically normal in GCT, revealed LOH of 11 and 5%, respectively. We also observed a LOH of 22% in the TP53 gene, despite the fact that mu tations in TP53 do not occur in testis cancer. Since a high frequency of LOH at DCC (18q21.3) occurs equally at all histological subsets in GCT, we conclude that the loss of the function of this gene is an earl y event in testicular GCTs. However, the observed LOH levels at APC/MC C (5q21), RE (13q14), and WT-1 (11p13) could represent a functional lo ss of the corresponding tumor suppressor gene in some GCTs or reflect the loss of sequences in the same general chromosome region but involv ing a different tumor suppressor locus. Therefore, detailed mapping of these chromosomes is required to define the precise locations of maxi mal LOH in testis cancer.