%0 Journal Article
%T An epigenomic mechanism in retinoblastoma: the end of the story?
%A A Linn Murphree
%A Timothy J Triche
%J Genome Medicine
%D 2012
%I BioMed Central
%R 10.1186/gm314
%X The identification of the retinoblastoma gene RB1 in 1986 [1] and the discovery of its pivotal role in cell cycle control thrust RB1 and its associated disease, retinoblastoma, to the forefront of cell and cancer biology. Inactivation of both alleles of RB1 is a hallmark of retinoblastoma, a rare but aggressive childhood cancer of the retina. Today, 26 years since the identification of RB1, the primary treatment of newly diagnosed retinoblastoma consists of systemic or regional chemotherapy, or enucleation (surgical removal of the eye). These approaches do not make the most of our vast knowledge of RB1.The lack of new therapies, despite extensive characterization of the RB1 gene and its manifold functions, is likely to be due to rapid progression of malignancy changes that occur in intraocular retinoblastoma after tumor initiation. As clinicians and pathologists we directly observe a panoply of physical changes occurring inside an eye affected by retinoblastoma. Newly arising tumors, usually discovered in the retinas of infants with a family history of the disease, are always the same - small, soft, round, intraretinal, gray-white 'clones' - as if they were daughter cells arising from a single cell with identical growth characteristics. As these 'clones' grow, asymmetrical overgrowth appears, which may be due to clonal growth advantages, followed by focal 'nipples' that shed clumps and strings of cells into the vitreous or subretinal space. This intraocular dispersal of tumor cells is associated with further adjustment to hypoxia, allowing massive tumor growth independently of an obvious vascular supply. Eventually, as the eye fills with tumor mass, cells invade both adjacent tissues, the choroid and the optic nerve, signaling to the pathologist an increased risk to the child of metastatic disease. The molecular mechanism(s) behind these consistently observed phenotypic alterations are not understood. In light of recent findings, however, this may be about to change
%U http://genomemedicine.com/content/4/2/15