IOTH ANNIVERSARY ARTICLE Pathogenesis of Adult Tesficular Germ Cell Tumors A Cytogenetic Model Bauke de Jong, J. Wolter Oosterhuis, S~rgio M. M. J. Castedo, AnneMarie Vos, and Gerard J. te Meerman ABSTRACT: In essence, two models exist of the pathogenetic relationship between seminomas and nanseminomatous germ cell tumors (NSGCTs). In the first model, the histogenesis of seminomas is assumed to diverge from that of the other testicular germ cell tumors (TGCTs) at an early stage. The neoplastic pathway of seminomas and NSGCTs is different, with limited or no crossover. The second model suggests that seminomas and NSGCTs have a common origin with a single neoplastic pathway on which seminomas are an intermediate stage in development of NSGCTs. Our data on the cytogenetics and ploidy of seminomas, combined tumors, and NSGCTs lend support to the model of pathogenesis of seminomas and NSGCTs in which all TGCTs (with the possible exception of spermatocytic seminoma and infantile yolk sac tumor) have a single origin and neoplastic pathway, with seminomas representing an intermediate stage in develop- ment of NSGCT components, as opposed to the model in which seminomas and NSGCTs develop separately. The progression of TGCTs probably proceeds from high to lower numbers of chromosomes and is therefore accompanied by a net loss of chromosomal material. This decrease will be the end result of loss of specific chromosomes, gain of some other chromosomes (or part of chromosomes), and development of structural abnormalities. INTRODUCTION A model of the pathogenesis of testicular germ cell tumors (TGCTs) of adults is presented. The model is based on our own observations and those of other investiga- tors of DNA index (DI), chromosome numbers, and specific structural chromosomal abnormalities in TGCTs. Most of our cytogenetic data have been published. For a full description and discussion of these data, in particular of structural chromosomai abnormalities, the reader should consult our previous publications. From the Departments of Human Genetics (B. d. J., S. M. M. J. C., A. M. V., G. J. t. M.), and Pathology (J. W. O., S. M. M. I. C.), University of Groningen, Groningen. The Netherlands. Address reprint requests to: Bauke de Jong, Ph.D., Department of Human Genetics, Ant. Deusinglaan 4, 9713 AW Groningen, The Netherlands. S. M. M. J. C. is a member of the staff of the Department of Medical Genetics, University of Oporto, Portugal. Received November 17, 1989; accepted November 30, 1989. 143 © 1990 Elsevier Science Publishing Co., Inc. Cancer Genet Cytogenet 48:143-167 (1990) 655 Avenue of the Americas, New York, NY 10010 0165-4608/90/$03.50