Expression of ID genes in differentiated elements of human male germ cell tumors

The ID genes are members of a family of genes that encode helix-loop-helix (HLH)-containing proteins. The Id proteins, unlike other HLH proteins, lack an adjacent DNA binding domain and hence act as dominant negative regulators of HLH transcription factors that have been implicated in control of cellular differentiation. Although the role of Id genes in murine development has been documented, their roles in human embryogenesis remain unknown. In this study, human male germ cell tumors (GCTs) were used as a model for examining the expression of the ID genes in various histologies that are reflective of different temporal phases of human development. In seminomas, little or no expression of IDI, ID2, and ID3 was detected, consistent with the uncommitted germ cell-like phenotype of this tumor histology. Likewise, GCTs with histologies reflective of extraembryonic and embryonic patterns of differentiation exhibited patterns of expression of the three ID genes often similar to those noted during murine development. It was also evident, as revealed by ID expression patterns, that despite the overall aberrant spatial differentiation patterns displayed by these tumors, some tissue-tissue interactions reminiscent of those observed during normal embryogenesis are retained. Thus, adult male GCTs offer a unique system in which the role of genes such as the IDs can be studied in human embryogenesis.