Download or read book The Molecular Progression from Retina Through Retinoma to Retinoblastoma and the Role of the P75 subscript N subscript T subscript R Neurotrophin Receptor written by Helen Dimaras and published by . This book was released on 2007 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Retinoblastoma, a childhood cancer of the retina, is initiated by the loss of RB1; genomic gains of oncogenes (KIF14, DEK, E2F3, MYCN) and loss of tumor suppressor genes (CDH11) are essential for malignant progression. These genes are not involved in apoptosis, the disruption of which is thought to be a hallmark of tumorigenesis. A gene that may play such a role is p75NTR, which functions in retinal apoptosis. Retinoma, a benign retinal tumor, is also associated with mutation of RB1, however it is unknown if its development requires additional somatic inactivation of the second RB1 allele or additional disruption of the downstream retinoblastoma-associated candidate genes. In this thesis, I looked at a potential role for p75NTR in retinoblastoma and retinoma development, and analyzed the status of RB1 in retinoma. Retinoma results after complete RB1 loss, but prior to p75NTR loss, evident only in retinoblastoma. Unlike retina or retinoblastoma, retinoma expresses senescence marker p16 INK4a. Expression of candidate retinoblastoma oncogenes and tumor suppressor genes is not similarly altered in retinoma. Early, but not advanced, tumors from the TAg-RB murine retinoblastoma model expressed p75NTR, which was also correlated with expression of apoptosis marker activated caspase-3. A retinoblastoma model that lacked p75NTR at the onset of TAg-RB development displayed lager tumor area at equivalent stages as the TAg-RB mouse, presumably due to a decrease in apoptosis during the early stages of tumor development. In conclusion, retinoma is a senescent RB1-/- precursor to retinoblastoma, only progressing to full retinoblastoma after the disruption p75NTR and senescence, leading to the subsequent specific changes highlighted in this study.