MODL-30. AN ENGINEERED TRANSGENIC MOUSE MODEL OF RETINOBLASTOMA

Abstract Retinoblastoma, the most common intraocular tumor of childhood, was recently shown to comprise two major molecular subtypes. Subtype 1 includes heritable forms, with germline mutation RB1 and a cone-differentiated state. 2 is often non-hereditary, exhibits stemness features, increased expression MYCN its target genes, high risk metastasis. Relative subtype 1, tumors have worse prognosis. To date, no mouse model has been available for studying disease. It known that SHH pathway proteins including SHH, GLI1 GLI2 are abnormally elevated in human retinoblastoma. We discovered activation developing retina leads exhibit cellular features resembling retinoblastoma aberrant upregulation genes. Because downstream pathway, we hypothesize inhibiting SHH-GLI2-MYCN signaling axis may effectively treat Using our based retinoblastoma, will elucidate mechanisms underlying initiation progression, evaluate therapeutic potential inhibitors preventing validate findings using cell lines patient-derived xenografts. Our studies yield new mechanistic insights into development identify novel targets early detection, treatment, prevention ocular associated metastatic