Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma

Lauren E. Hudson, Pia Mendoza, William H. Hudson, Alison Ziesel, G. Baker Hubbard, Jill Wells, Bhakti Dwivedi, Jeanne Kowalski, Sandra Seby, Viren Patel, Eldon Geisert, Charles Specht, Hans E. Grossniklaus

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2328-2338
Number of pages11
JournalAmerican Journal of Pathology
Volume188
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Anaplasia
Retinoblastoma
Transcriptome
Nuclear Pore Complex Proteins
Genes
Gene Expression
Microarray Analysis
Genetic Markers
Neoplasms
Morbidity
Mortality
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Hudson, L. E., Mendoza, P., Hudson, W. H., Ziesel, A., Hubbard, G. B., Wells, J., ... Grossniklaus, H. E. (2018). Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma. American Journal of Pathology, 188(10), 2328-2338. https://doi.org/10.1016/j.ajpath.2018.06.013
Hudson, Lauren E. ; Mendoza, Pia ; Hudson, William H. ; Ziesel, Alison ; Hubbard, G. Baker ; Wells, Jill ; Dwivedi, Bhakti ; Kowalski, Jeanne ; Seby, Sandra ; Patel, Viren ; Geisert, Eldon ; Specht, Charles ; Grossniklaus, Hans E. / Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma. In: American Journal of Pathology. 2018 ; Vol. 188, No. 10. pp. 2328-2338.
@article{763fbf0bccf74f0c884e246e87614e0f,
title = "Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma",
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.",
author = "Hudson, {Lauren E.} and Pia Mendoza and Hudson, {William H.} and Alison Ziesel and Hubbard, {G. Baker} and Jill Wells and Bhakti Dwivedi and Jeanne Kowalski and Sandra Seby and Viren Patel and Eldon Geisert and Charles Specht and Grossniklaus, {Hans E.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1016/j.ajpath.2018.06.013",
language = "English (US)",
volume = "188",
pages = "2328--2338",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "10",

}

Hudson, LE, Mendoza, P, Hudson, WH, Ziesel, A, Hubbard, GB, Wells, J, Dwivedi, B, Kowalski, J, Seby, S, Patel, V, Geisert, E, Specht, C & Grossniklaus, HE 2018, 'Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma', American Journal of Pathology, vol. 188, no. 10, pp. 2328-2338. https://doi.org/10.1016/j.ajpath.2018.06.013

Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma. / Hudson, Lauren E.; Mendoza, Pia; Hudson, William H.; Ziesel, Alison; Hubbard, G. Baker; Wells, Jill; Dwivedi, Bhakti; Kowalski, Jeanne; Seby, Sandra; Patel, Viren; Geisert, Eldon; Specht, Charles; Grossniklaus, Hans E.

In: American Journal of Pathology, Vol. 188, No. 10, 01.10.2018, p. 2328-2338.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma

AU - Hudson, Lauren E.

AU - Mendoza, Pia

AU - Hudson, William H.

AU - Ziesel, Alison

AU - Hubbard, G. Baker

AU - Wells, Jill

AU - Dwivedi, Bhakti

AU - Kowalski, Jeanne

AU - Seby, Sandra

AU - Patel, Viren

AU - Geisert, Eldon

AU - Specht, Charles

AU - Grossniklaus, Hans E.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85053761607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053761607&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2018.06.013

DO - 10.1016/j.ajpath.2018.06.013

M3 - Article

C2 - 30036517

AN - SCOPUS:85053761607

VL - 188

SP - 2328

EP - 2338

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 10

ER -

Hudson LE, Mendoza P, Hudson WH, Ziesel A, Hubbard GB, Wells J et al. Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma. American Journal of Pathology. 2018 Oct 1;188(10):2328-2338. https://doi.org/10.1016/j.ajpath.2018.06.013