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Item The genomic landscape of retinoblastoma: a review(Wiley Blackwell (Blackwell Publishing), 2014-01) Thériault, Brigitte L.; Dimaras, Helen; Gallie, Brenda L.; Corson, Timothy W.; Department of Ophthalmology, IU School of MedicineRetinoblastoma is a paediatric ocular tumour that continues to reveal much about the genetic basis of cancer development. Study of genomic aberrations in retinoblastoma tumours has exposed important mechanisms of cancer development and identified oncogenes and tumour suppressors that offer potential points of therapeutic intervention. The recent development of next-generation genomic technologies has allowed further refinement of the genomic landscape of retinoblastoma at high resolution. In a relatively short period of time, a wealth of genetic and epigenetic data has emerged on a small number of tumour samples. These data highlight the inherent molecular complexity of this cancer despite the fact that most retinoblastomas are initiated by the inactivation of a single tumour suppressor gene. This review outlines the current understanding of the genomic, genetic and epigenetic changes in retinoblastoma, highlighting recent genome-wide analyses that have identified exciting candidate genes worthy of further validation as potential prognostic and therapeutic targets.Item Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma(Molecular Vision, 2015) Wenzel, Andrea A.; O'Hare, Michael N.; Shadmand, Mehdi; Corson, Timothy W.; Department of Ophthalmology, IU School of MedicinePURPOSE: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development. METHODS: The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis. RESULTS: Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous. CONCLUSIONS: OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.