Genomic imprinting and carcinogenesis

The Mendelian inheritance is based on the fundamental rule in which mammalian genes are expressed equally from two homologous biparental alleles. Recently a small number of genes have been identified to show an exception to this rule in that homologous alleles can function differently in somatic cells depending on whether they come from the mother or the father. This intriguing biological phenomenon is called as genomic imprinting which does not conform classical Mendelian inheritance and has potentially far reaching implications for genetics, evolution, developmental biology and pathology including cancer. The gene encoding insulin-like growth factor 2 (IGF2) harbors at 11p15.5 and serves as paradigm for an imprinted gene. The IGF2 gene has been demonstrated to be imprinted with the paternal allele expressed and the maternal being silent which is evolutionally conserved between mice and human. Loss of imprinting (LOI) of IGF2 has been demonstrated in a dozen of tumor types including Wilms tumor (WT) with a promise of many more to come. The LOI of IGF2 may induce increased or deregulated IGF2 expression which could initiate the onset of WT. Thus the LOI of IGF2 may provide a novel mechanism of gene activation and play a role in the development of a wide range of tumors. This review also discusses other imprinted genes on 11p15 which may have a role in WT or other diseases. Finally molecular mechanisms of genomic imprinting are discussed.