Epigenetic models for tumor formation assume that oncogenic transformation results from changes in the activity of otherwise normal genes. Since gene activity can be inhibited by DNA methylation, and inactivation of tumor suppressor genes is a fundamental process in oncogenesis, we investigated the methylation status of the retinoblastoma suppressor gene (RB gene) on chromosome 13, in blood and tumor cells from 21 retinoblastoma patients. Using methylation-sensitive restriction enzymes and a cloned DNA probe for the unmethylated CpG island at the 5' end of RB gene, we obtained evidence of hypermethylation of this gene in a sporadic unilateral retinoblastoma tumor. The closely linked esterase D gene and a CpG-rich island on chromosome 15 were not affected. We suggest that changes in the methylation pattern of the RB gene play a role in the development and spontaneous regression of some retinoblastoma tumors.

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These results support the view that the pathogenesis of CSC is related to an increase in the sympathetic activity of the autonomic nervous system. Furthermore, the LF/HF ratios seem to correlate with the activity of the disease.

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Fifty-six globes that had to be enucleated following ruthenium plaque therapy were examined histopathologically. These eyes account for 10% of all uveal melanomas treated at the University Eye Clinic Essen up until 1985. All but one revealed at least some supposedly viable tumor cells. The most prominent findings within the tumors were tumor cell necrosis, vacuolization and balloon cell degeneration, vascular obstruction and fibrosis of the tumor stroma with accumulation of pigmented macrophages. Tumor necrosis was complete or nearly complete in five cases. Tumor regression correlated with cell type and pigmentary characteristics of the tumor, with epithelioid and heavily pigmented tumor cells being more radiosensitive. Tumor regression was inhomogeneous, possibly due to polyclonality, with tumor cells of varying radiosensitivity, or due to patchy areas of vascular obliteration. Among other ocular structures, extensive subretinal gliosis, chorioretinal atrophy and scarring of the sclera within the field of radiation were observed. Scleral necrosis was present in only five cases and was limited to areas in which the tumor had infiltrated the deep scleral layers. The findings described were considered to reflect radiation injury rather than spontaneous tumor regression when compared to 70 control eyes that had been enucleated without prior treatment for uveal melanoma.