Genomic imprinting and cancer.

Imprinting is vital for normal development, and disruption of imprinting mechanisms on syntenic chromosomes gives very similar phenotypes in mouse and humans. In addition, disruption of normal imprinting provides a plausible explanation for preferential LOH in some embryonal tumours. Moreover, there is evidence that in Wilms' tumour, dysregulation of specific imprinted genes may give rise to the cancer phenotype. Many more questions regarding genomic imprinting need to be answered before the associations described in this review can be properly understood. The most basic issues, such as when and how the imprint is established, can still only be speculated upon. Further study of new imprinted genes and the relationship between their domains and differential replication may show us higher control mechanisms than methylation alone. It remains to be seen if these epigenetic modifications are amenable to therapeutic change in the treatment of inherited syndromes and cancer, or if they can be used to assess individuals at risk of disease. Until then it is probably unwise to speculate on a single unifying theory that explains why a subset of the genome shows such a peculiar non-Mendelian form of inheritance.