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 certain human genes, e.g. the paternally-H19 and the maternally-imprinted 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. trophoblastic diseases, and their maternal counterpart, i.e. ovarian teratomas, are associated with apparent relaxation of imprinting once they turn malignant. Paediatric neoplasms, like Wilm's tumor (WT) and rhabdomyosarcoma, often express IGF2 and H19. Recently, we have found H19 expression 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 tumor preferential paternal allele retention and chromosome 11 short arm physical linkage with oncogenes like H-ras, we hypothesize that imprinted genes not only accompany cancer but may play a causative role as well.
Biran
H
H
Department of Biochemistry, Hebrew University, Jerusalem, Israel.
Ariel
I
I
De Groot
N
N
Hochberg
A
A
D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002648:Child; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D016162:Genes, Wilms Tumor; D011905:Genes, ras; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D011247:Pregnancy; D009396:Wilms Tumor / Q000235:genetics; D000509:alpha-Fetoproteins / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D000509:alpha-Fetoproteins; C031192:oncofetal antigens; D007335:Insulin-Like Growth Factor II