A molecular model for the development of germ cell cancer

Human germ cell tumors comprise a heterogeneous group of neoplasms. Those of the adult testis, known as TGCTs, originate from carcinoma in situ (CIS), which are initiated during intra-uterine development. We present here a molecular model for the development of TGCTs, including various parameters, such as apoptosis, chromosomal constitution, as well as genomic imprinting. We assume that TGCTs originate from a pluripotent, erased embryonic germ cell, of which aneuploidization is one of the early events. Subsequently, net loss and gain of specific chromosomal regions result in the consistent pattern of chromosomal aberrations that are observed in these tumors, including gain of 12p-sequences. By means of analysis of a relatively small region of the short arm of chromosome 12, we are in the process of identifying the relevant genes. Possibly, this gene(s) suppresses apoptosis outside the specific micro-environment of the seminiferous tubule.