Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma

• Type of Material: Article
• Authors: Lauren E. Hudson, Emory University; Pia Mendoza, Emory University; William Hudson, Emory University; Alison Ziesel, Emory University; George Hubbard, Emory University; Jill Wells, Emory University; Bhakti Dwivedi, Emory University; Jeanne Kowalski, Emory University; Sandra Seby, Emory University; Viren Patel, Emory University; Eldon Geisert Jr, Emory University; Charles Specht, Penn State Milton S. Hershey Medical Center; Hans Grossniklaus, Emory University
• Language: English
• Date: 2018-10-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Society for Investigative Pathology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ajpath.2018.06.013
• Title of Journal or Parent Work: American Journal of Pathology
• ISSN: 0002-9440
• Volume: 188
• Issue: 10
• Start Page: 2328
• End Page: 2338
• Grant/Funding Information: Supported by National Eye Institute grant NEI P30EY06360 (H.E.G.) and a grant from Research to Prevent Blindness.
• Keywords: INTERNATIONAL CLASSIFICATION; INVASION; Life Sciences & Biomedicine; COMPLEX; R-PACKAGE; LECTURE; ENUCLEATED EYES; INTRAOCULAR RETINOBLASTOMA; CLINICAL RISK-FACTORS; PROMOTER; Science & Technology; INTRAARTERIAL CHEMOTHERAPY; Pathology
• Research Categories: Health Sciences, Oncology; Chemistry, Biochemistry

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.