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• W4362526036 abstract "Abstract Our recent investigations unveiled the transcriptional and translational loss of Retinal degeneration Protein 3 in neuroblastomas (NB) when compared to the healthy adult and fetal tissues. Further, our preclinical studies with patient derived cellular systems and mouse model of high-risk NB (HR-NB) demonstrated that RD3 loss orchestrates disease progression. More importantly, we defined the therapy pressure driven acquired loss of RD3 in neuroblastomas, its crucial function in the evolution of progressive disease (PD), and further defined the prognostic and predictive significance of RD3 loss in NB. In this study, we investigated the use of RNAScope as a sensitive and specific method for the evaluation of spatiotemporal RD3 transcriptional loss in NB. We investigated the expression of RD3 mRNA in FFPE NB (n = 100) tissues utilizing RNAScope with custom archived RD3 specific probes comparing it with the matched RD3 protein (IHC) expression patterns. With positive (PPIB) and negative (DapB) controls in place, our results displayed definite and specific RD3 mRNA expression in NB. We observed a statistically significant association of RD3 mRNA loss to the disease progression and poor clinical outcomes. Further, we observed significant correlation to the loss of RD3 transcription to the evolution of progressive disease. More importantly, the expression gradients of RD3 mRNA observed with RNAScope assay (compared in terms of no treatment vs progressive disease, primary vs metastatic disease, relapsed vs no relapse, favorable to unfavorable disease) illustrate the concordance with the RD3 IHC outcomes. Our results provide a reference basis for better RD3 mRNA readouts in NB, and more importantly identify the technically sound, adaptable (high throughput/single event, manual/automatic) RNAScope in situ hybridization assay as an alternate approach to detect spatiotemporal expression of RD3 mRNA. Together, the results provide a new, descriptive, and efficient platform, RNAScope for assessing spatiotemporal RD3 mRNA expression that could better inform disease prognosis and therapy response in children with NB. Funding: This work was partially or in full, funded by Department of Defense DoD-CA210339 and Oklahoma Center for the Advancement of Science and Technology, OCAST-HR19-045. Citation Format: Dinesh Babu Somasundaram, Sheeja Aravindan, Zhongxin Yu, Ashley Baker, Natarajan Aravindan. RNAScope in situ hybridization as a novel approach for the spatiotemporal assessment of RD3 mRNA expression in neuroblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6722." @default.
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• W4362526036 date "2023-04-04" @default.
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• W4362526036 title "Abstract 6722: RNAScope <i>in situ</i> hybridization as a novel approach for the spatiotemporal assessment of RD3 mRNA expression in neuroblastoma" @default.
• W4362526036 doi "https://doi.org/10.1158/1538-7445.am2023-6722" @default.
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