Loss of Imprinting ofIGF2as an Epigenetic Marker for the Risk of Human Cancer

Abstract

IGF2is the first gene discovered to be imprinted and expressed exclusively from the paternal allele in both human and mouse.IGF2is also the first imprinted gene displaying loss of imprinting (LOI) or aberrant imprinting in human cancers. Evidently, LOI or reactivation of the maternal allele ofIGF2is associated with an increase ofIGF2expression that may subsequently play an important role in the onset of human cancers. The most important discovery was the association of LOI ofIGF2with the risk of developing human colorectal cancer. LOI occurs not only in colon cancer tissues, but also in matched normal tissues and peripheral blood cells. A pilot study indicated a significant relationship between LOI ofIGF2and family history as well as personal history of colorectal cancer, suggesting that LOI ofIGF2might be a valuable biomolecular marker of predicting an individual's risk for colon cancer. A recent epigenetic progenitor model suggested that human cancers might have a common basis that involves an epigenetic disruption of progenitor cells mediated by “tumor progenitor genes” and proposed that non-neoplastic but epigenetically disrupted progenitor cells might be an important target for cancer risk assessment and prevention.