FREQUENT P16INK4 (MTS1) GENE INACTIVATION IN TESTICULAR GERM-CELL TUMORS

The molecular mechanisms responsible for the development of testicular germ cell tumors (GCTs) have not as yet been elucidated. The aim of t he present study was to determine whether genetic alterations of p16(I NK4) (MTS1) and/or cyclin-dependent kinase 4 (CDK4) occur in the genes is of these tumors. We have analyzed these two genes in 29 testicular GCT's, seminomas, and nonseminomas, None of the tumors showed either p 16(INK4) or CDK4 mutations. Only 1 of the 29 GCTs displayed loss of he terozygosity of the p16(INK4) gene. No homozygous deletions of p16(INK 4) were detected. Evidence of hypermethylation of p16(INK4) exon 1, ho wever, was demonstrated in 13 of the 26 (50%) GCTs analyzed. Tumor sam ples having exon 1 of p16(INK4) methylated expressed significantly low er levels of p16(INK4) mRNA, as analyzed by reverse transcriptase poly merase chain reaction. These results suggest that p16(INK4) inactivati on plays a role in the genesis of GCTs.