Retinoblastoma as an Epigenetic Disease A Proposal 外文参考文献.doc

Journal of Cancer Therapy, 2011, 2, 362-371 doi:10.4236/jct.2011.23049 Published Online August 2011 (http://www.SciRP.org/journal/jct) Retinoblastoma as an Epigenetic Disease: A Proposal Domenico Mastrangelo, Cosimo Loré, Giovanni Grasso Department of Biomedical Sciences, University of Siena, Siena, Italy. Email: mastrangelo@unisi.it Received May 6 , 2011; revised July 15 , 2011; accepted July 25 , 2011. th th th ABSTRACT The aim of the present review is to give 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, as applied to the interpretation of clinical , epidemiological and biological data in retinoblastoma, can not only explain the inconsistencies of the mutational (“two hit”) model, but also opens new outstanding scenarios in the fields of diagnosis , treatment and prevention of this eye tumour. This review is both a collection of literature data arguing against the role of the mutational (“two hit”) model in the genesis of retinoblastoma , and a documented evaluation of how the Epigenetic , rather than the genetic model fit the variegated phenotypic expression of the disease. 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 reti- noblastoma in young children. Environmental toxicants, including radiations, wrong diets, and infectious diseases, among others, all play a major role in conditioning the degree of DNA methylation in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which, on the other hand, can be