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Pia R. Mendoza, Eldon E Geisert, Alison C Ziesel, Charles S Specht, G Baker Hubbard, Jill R Wells, Hans E Grossniklaus; Gene Expression Profiling of Retinoblastoma and Retinocytoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3444. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We hypothesize that tumor growth in retinoblastoma involves the differential expression of genes associated with retinal development, cellular differentiation, and cell cycle regulation. Genetic alterations in retinoblastoma are associated with histopathologic characteristics relating to tumor behavior and clinical outcomes. The objectives of this study are to compare the gene expression profiles of retinoblastoma, retinocytoma, and normal retina using microarray data and to determine the expression profiles that correlate with clinical and histologic features.
This retrospective clinicopathologic study involved the review of demographic, clinical, and histopathologic findings from 33 patients who underwent primary enucleation for retinoblastoma, 3 of which had retinocytoma components and 2 with matched normal retinal tissue. Gene expression profiling was conducted on RNA isolated from formalin-fixed paraffin embedded tissue. For the array data analysis, hierarchical clustering analysis and principal component analysis (PCA) were done, with Pearson correlation and average linkage clustering. Differentially expressed genes were identified using SAM (Significance Analysis of Microarrays) with a q-value or false discovery cutoff at 5%. Functional annotation of differentially expressed genes through gene ontology was performed.
Principal component analysis shows clustering of samples by 3 groups: retinoblastoma, retinocytoma, and normal retina. Analysis of only the retinoblastoma samples shows clustering of tumors with mild, moderate, and severe anaplasia. Unsupervised hierarchical clustering reflected groupings similar to those obtained by PCA. Highly enriched gene ontology categories were those associated with photoreceptor differentiation and phototransduction in normal retina, transcription regulation and nuclear organization in retinocytoma, and cell cycle and mitosis in retinoblastoma.
Gene expression profiling demonstrates differential expression between normal retina, retinocytoma, and retinoblastoma. Progression from retinocytoma to retinoblastoma may be secondary to compromised gene regulation and expression resulting in modifications in nuclear organization manifested phenotypically as cellular anaplasia.
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