Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis

Chromosomal information on germ cell tumors of the infantile testis, ie, te ratomas and yolk sac tumors, is limited and controversial. We studied two t eratomas and four yolk sac tumors using comparative genomic hybridization ( CGH) and in situ hybridization. No chromosomal anomalies were found in the teratomas by any of the methods, not even after CGH on microdissected tumor cells. All yolk sac tumors showed aneuploidy, loss of parts of 4q and 6q, and gain of parts of 20q. Underrepresentation of parts of 8q and overrepres entation of parts of 3p, 9q, 12p, 17, 19q, and 22 were detected in most cas es. In addition, one recurrent yolk sac tumor after a sacral teratoma was s tudied, showing a highly similar pattern of imbalances. While CGH demonstra ted loss of 1p36 in one testicular yolk sac tumor, in situ hybridization re vealed loss of this region in all yolk sac tumors. High-level amplification of the 12q13-q14 region was found in one yolk sac tumor. MDM2, of which th e encoding gene maps to this chromosomal region, was found in all cases usi ng immunohistochemistry, whereas no p53 could be detected. Accordingly, no mutations within exons 5 to 8 of the p53 gene were observed. These data pro ve the absence of gross chromosomal aberrations in teratomas of the infanti le testis and show a characteristic pattern of gains and losses in the yolk sac tumors. Besides confirmation of previously found anomalies, recurrent losses of 1p21-31 and 4q23-33 and gains of 9q34 and 12p12-13 have not been reported before. While genetic inactivation of p53 seems unimportant in the pathogenesis of these tumors, biochemical inactivation by MDM2 might be in volved. These data support the existence of three entities of germ cell tum ors of the human testis: teratomas and yolk sac tumors of infants, seminoma s and nonseminomas of adolescents and young adults, and spermatocytic semin omas of the elderly, each with its own specific pathogenesis.