Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part due to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to easily assess tumor samples for degree of anaplasia. Instead, identification of genetic signatures able to distinguish among anaplastic grades and thus predict high versus low risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia would also yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes are also able to accurately predict severe anaplasia in our dataset. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

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Hudson LE, Mendoza P, Hudson WH, Ziesel A, Hubbard GB 3rd, Wells J, Dwivedi B, Kowalski J, Seby S, Patel V, Geisert E, Specht C, Grossniklaus HE