The stem cell identity of testicular cancer

Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor formation and the relationship between germ cell tumorigenesis and stem cell biology will be presented.