Genetic Studies of a Surgically Resected Retinal Capillary Hemangioma From a Patient Without a Von Hippel–Lindau Germ Line Mutation.

Abstract

Abstract: : Purpose: To compare the von Hippel–Lindau (VHL) gene sequence in DNA isolated from peripheral leukocytes and cells derived from a retinal capillary hemangioma (RCH) that was surgically excised en bloc from a patient with unilateral disease. Methods: The tumor was resected by adapting standard pars plana vitrectomy techniques to include ligation of feeder vessels and endodiathermy to limit bleeding upon tumor removal. Standard pathological examination with H and E staining was performed. Peripheral blood was processed by the Children’s Hospital of Philadelphia Molecular Genetics Laboratory and included standard methods of DNA extraction, polymerase chain reaction, gel electrophoresis and DNA sequencing. Tumor tissue was cultured in either Media 131 or RPMI to allow tumor cells to attach and proliferate. Results: There is no family history of VHL disease or any of its’ associated tumors. A complete medical examination for other VHL–associated tumors was negative. No disease causing mutations were identified in any of the3 exons of the VHL gene in DNA from peripheral leukocytes. Molecular analysis of the VHL gene in DNA from tumor cells is underway. Pathologic examination was consistent with a diagnosis of RCH. Conclusions: VHL is a dominantly inherited disease in which the loss of a tumor suppressor leads to a high rate of formation of different tumors, the most common of which is RCH. However, the prevalence of truly sporadic RCH is unclear. The VHL gene has been analyzed from tumors recovered after either enucleation or cadaveric donation, but only from individuals known to have a germ line VHL mutation. Analysis of the tumor cell line or the tumor itself will either verify that this RCH arose from two events to cause loss in VHL protein function or a novel mechanism is involved in the evolution of this particular RCH.

Keywords: retina • tumors • genetics