The Epigenetic Origin of Retinoblastoma

The aim of the present review is to give new insights into the pathogenesis of retinoblastoma, by applying the principles of epigenetics to the study of clinical, epidemiological and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, epigenetics, can not only explain the inconsistencies of the mutational (‘two hit’) model in the genesis of retinoblastoma, but also open new outstanding scenarios in the fields of diagnosis, treatment and prevention of this eye tumour and cancer in general. After more than four decades of predominance of the ‘genetic’ theory, this review represents, to the authors’ knowledge, the first attempt to look at retinoblastoma from the point of view of epigenetics. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasises the role of environment and its interactions with the genome, in generating retinoblastoma in young children. Environmental toxicants, including, among others, radiations, wrong diets and infectious diseases, all play a major role in conditioning the degree of DNA methylation (one of the leading mechanisms of epigenetic gene regulation) in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which can 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.