Vladusic T et al. / Tumor suppressor genes in testicular germ cell tumors 173 a synergistic effect, which imposes a stronger selec- tive pressure for the cellular transformation. This may also help to explain the high proliferation rate and/or invasiveness of TGCTs with embryonal car- cinoma and yolk sac tumor component. A higher incidence of LOH in nonseminomas may provide a clue to their invasive behavior, because for some of the nonseminoma types there seem to be a re- gion of preferential loss (3q27–3q28 in embryonal carcinoma), and all of the TGCTs show gain of 12p11–12p12 sequences.20 Knowing the exact na- ture of genetic alterations associated with these tumors may provide novel treatment strategies.28 However, the low frequency of observed LOHs in this study could be a consequence of genomic instability in above mentioned nonseminomas, rather than the main cause of CDKN2A and RB1 inactivation.24 Acknowledgments This work was supported by Grant 058-0582261- 2246 from Ministry of Science and Technology, Republic of Croatia. References 1. Fombonne J, Devouassoux-Shisheboran M, Bouvier R, Droz J-P, Benahmed M, Krantic S. Analysis of p16INK4A gene promoter in male germ-cell tumors: identification of a new point mutation. Cancer Detect Prev 2005; 29: 1-7. 2. 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