ANALYSIS OF THE DCC TUMOR-SUPPRESSOR GENE IN TESTICULAR GERM-CELL TUMORS - MUTATIONS AND LOSS OF EXPRESSION

Inactivation of the DCC (Deleted in Colon Carcinoma) tumor suppressor gene by allelic loss and/or reduced expression is associated with the development of colon cancer, gliomas, gastric and prostatic malignanci es. In a total cohort of 51 testicular germ cell tumors (GCT) of diffe rent histologies we analyzed restriction fragment length polymorphism (RFLP) for DCC at two specific DNA sites in 37 GCT and DCC mRNA expres sion compared to that of the adjacent normal testicular tissue in 41 G CT, one Leydig cell tumor and one testicular metastasis of a non-small cell lung cancer (NSCLC). Two of 17 tumors (11.7%) informative for th e Msp I polymorphic site of the DCC gene and 6/25 tumors (24.0%) infor mative for variable number of tandem repeat (VNTR) showed loss of hete rozygosity (LOH). DCC expression was analyzed by semi-quantitative pol ymerase chain reaction after initial reverse transcription (RT-PCR). T hirty of 41 GCT (73.1%) and both, the Leydig cell tumor and the testic ular metastasis of NSCLC, had a nearly complete or total loss of DCC m RNA expression. Six of 11 (54.5%) seminomas and 24/30 (80.0%) nonsemin omas had this loss of expression. Twelve of 17 (70.5%) localized tumor s, 9/13 (69.2%) tumors with lymph node involvement and 9/11 (82.2%) tu mors with distant metastases showed decreased or absent DCC expression . This data suggests that inactivation of the DCC gene, especially the loss of DCC expression, is associated with the development and progre ssion of human GCT.