Imprinted genes in liver carcinogenesis.

Each cell contains both maternal and paternal copies of all genes except those that reside on the sex chromosomes. However, because of a phenomenon termed genomic imprinting, not all genes are biallelically expressed. Imprinted genes play an important role in embryogenesis and recently have also been shown to be mechanistically involved in carcinogenesis. The growing list of imprinted genes implicated in tumor formation includes both a growth factor gene, insulin-like growth factor 2 (IGF2), and a receptor gene, mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R). Elevated expression of IGF2 is often found in tumors, and loss of imprinting is one mechanism by which its expression is deregulated. The M6P/IGF2R functions in the inactivation of the mitogen IGF2 and in the activation of the growth inhibitor, transforming growth factor beta. Recently, a high frequency of loss of heterozygosity with concomitant mutations in the remaining allele has been shown to occur at the M6P/IGF2R locus (i...