Abstract

Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

Original languageEnglish
Pages (from-to)506-515
Number of pages10
JournalRadiology
Volume288
Issue number2
DOIs
Publication statusPublished - Aug 2018

Cite this

Jansen, Robin W ; de Jong, Marcus C ; Kooi, Irsan E ; Sirin, Selma ; Göricke, Sophia ; Brisse, Hervé J ; Maeder, Philippe ; Galluzzi, Paolo ; van der Valk, Paul ; Cloos, Jacqueline ; Eekhout, Iris ; Castelijns, Jonas A ; Moll, Annette C ; Dorsman, Josephine C ; de Graaf, Pim. / MR Imaging Features of Retinoblastoma : Association with Gene Expression Profiles. In: Radiology. 2018 ; Vol. 288, No. 2. pp. 506-515.
@article{644fbdc527e74434a7603db88fd40a9b,
title = "MR Imaging Features of Retinoblastoma: Association with Gene Expression Profiles",
abstract = "Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58{\%}]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.",
author = "Jansen, {Robin W} and {de Jong}, {Marcus C} and Kooi, {Irsan E} and Selma Sirin and Sophia G{\"o}ricke and Brisse, {Herv{\'e} J} and Philippe Maeder and Paolo Galluzzi and {van der Valk}, Paul and Jacqueline Cloos and Iris Eekhout and Castelijns, {Jonas A} and Moll, {Annette C} and Dorsman, {Josephine C} and {de Graaf}, Pim",
note = "{\circledC} RSNA, 2018 Online supplemental material is available for this article.",
year = "2018",
month = "8",
doi = "10.1148/radiol.2018172000",
language = "English",
volume = "288",
pages = "506--515",
journal = "Radiology Now",
issn = "0033-8419",
publisher = "Radiological Society of North America Inc.",
number = "2",

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MR Imaging Features of Retinoblastoma : Association with Gene Expression Profiles. / Jansen, Robin W; de Jong, Marcus C; Kooi, Irsan E; Sirin, Selma; Göricke, Sophia; Brisse, Hervé J; Maeder, Philippe; Galluzzi, Paolo; van der Valk, Paul; Cloos, Jacqueline; Eekhout, Iris; Castelijns, Jonas A; Moll, Annette C; Dorsman, Josephine C; de Graaf, Pim.

In: Radiology, Vol. 288, No. 2, 08.2018, p. 506-515.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - MR Imaging Features of Retinoblastoma

T2 - Association with Gene Expression Profiles

AU - Jansen, Robin W

AU - de Jong, Marcus C

AU - Kooi, Irsan E

AU - Sirin, Selma

AU - Göricke, Sophia

AU - Brisse, Hervé J

AU - Maeder, Philippe

AU - Galluzzi, Paolo

AU - van der Valk, Paul

AU - Cloos, Jacqueline

AU - Eekhout, Iris

AU - Castelijns, Jonas A

AU - Moll, Annette C

AU - Dorsman, Josephine C

AU - de Graaf, Pim

N1 - © RSNA, 2018 Online supplemental material is available for this article.

PY - 2018/8

Y1 - 2018/8

N2 - Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

AB - Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

U2 - 10.1148/radiol.2018172000

DO - 10.1148/radiol.2018172000

M3 - Article

VL - 288

SP - 506

EP - 515

JO - Radiology Now

JF - Radiology Now

SN - 0033-8419

IS - 2

ER -