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Am J Pathol. 2018 Oct;188(10):2328-2338. doi: 10.1016/j.ajpath.2018.06.013. Epub 2018 Jul 21.

Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.

Author information

1
Department of Ophthalmology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
2
Department of Ophthalmology, Rollins School of Public Health, Emory University, Atlanta, Georgia; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
3
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia.
4
Winship Cancer Institute, Rollins School of Public Health, Emory University, Atlanta, Georgia.
5
Winship Cancer Institute, Rollins School of Public Health, Emory University, Atlanta, Georgia; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
6
Emory University Integrated Computational Core, Atlanta, Georgia.
7
Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
8
Department of Ophthalmology, Rollins School of Public Health, Emory University, Atlanta, Georgia; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia. Electronic address: ophtheg@emory.edu.

Abstract

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing 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 assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are 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 also would 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 also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

PMID:
30036517
PMCID:
PMC6168968
[Available on 2019-10-01]
DOI:
10.1016/j.ajpath.2018.06.013
[Indexed for MEDLINE]

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