Preferential Maternal LOH in the IGF2R Gene in Breast Cancer: Mutations And The Role Of Epigenetics

Tumors develop and progress as a result of alterations in oncogene and tumor suppressor genes. Knudson's two hit model predicts that cancer arises when both alleles of a tumor suppressor gene are inactivated. The insulin-like growth factor 2 receptor gene (IGF2R) is known to be a tumor suppressor for breast cancer,as mutations inactivating both alleles have been found in these tumors,consistent with its known functions in degradating insulin-like growth factor 2 (IGF2) and activating transforming growth factor ?1 (TGF- ?1),a growth inhibitor. Tumor suppressors can be inactivated by several means,such as genomic imprinting (a preferential silencing of a particular parental chromosome),large deletions resulting in loss of heterozygosity (LOH),and point mutations. In both humans and mice,IGF2R has gamete-of-origin dependent methylation which results in exclusive maternal expression in mice,while in humans imprinted expression is seen only in rare individuals and could be a predisposing factor for cancer. Since it is known that LOH plays a role in the genesis of breast cancer, we hypothesized that in some cases the event inactivating the other gene copy is parental imprinting. Read more