Retinoblastoma Epigenetics

The aim of the present chapter is to gi e new insights into the pathogenesis of retinoblastoma, by applying the principles of epigenetics to the analysis of clinical, epidemiological, and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, epigenetics, when applied to the interpretation of clinical, epidemiological, and biological data in retinoblastoma, can explain not only the inconsistencies of the mutational (“two hit”) model, but also open new outstanding scenarios in this fields of diagnosis, treatment and prevention of this eye tumor, and cancer in general. After more than four decades of predominance of the genetic theory, this chapter represents the first attempt to look at retinoblastoma from the point of view of epigenetics. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasizes the role of environment and the interaction of the environment with the genome, in generating retinoblastoma in young children. Environmental toxicants, including radiations, wrong diets, and infectious diseases, play a major role in conditioning the degree of DNA methylation (one of the leading mechanisms of epigenetic gene modulation) in embryos and fetuses during pregnancy, thus leading to stable, functional alterations of the genome, which, on the other hand, can also be transmitted from one generation to the next, thus mimicking a hereditary disease. An accurate analysis of the currently available literature on both retinoblastoma and epigenetics, coupled with the knowledge of the variegated phenotypic expression of the disease, can easily lead to the conclusion that retinoblastoma is an epigenetic, rather than a genetic disease. © Springer Science+Business Media B.V. 2012.