ON THE ONCODEVELOPMENTAL ROLE OF HUMAN IMPRINTED GENES

Genome imprinting has an essential role in normal embryonal mammalian development. Starting early in differentiation, the transcripts of cer tain human genes, e.g. the paternally-H-19 and the maternally-imprinte d IGF2, are expressed in specific tissues and organs during fetal life . In several malignant disorders, imprinted genes are, again, unfolded . Characteristically, expression follows the same tissue presentation as during embryogenesis. Clinical paternal disomies, i.e. trophoblasti c diseases, and their maternal counterpart, i.e. ovarian teratomas, ar e associated with apparent relaxation of imprinting once they turn mal ignant. Paediatric neoplasms, like Wilm's tumor (WT) and rhabdomyosarc oma, often express IGF2 and H-19. Recently, we have found H-19 express ion in invasive urothelial cancer. Evidently, imprinted genes display an oncodevelopmental mode of expression, very much like the classical oncofetal proteins AFP and CEA. Based on available data, including tum or preferential paternal allele retention and chromosome 11 short arm physical linkage with oncogenes like H-ras, we hypothesize that imprin ted genes not only accompany cancer but may play a causative role as w ell.