RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

Abstract

Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1). Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

Long Noncoding RNA LINC00202 Promotes Tumor Progression by Sponging miR-3619-5p in Retinoblastoma

“…Recently, lncRNAs have gained attention as their involvement in many physiological and pathological processes (Quinn and Chang, 2016). Accumulating literatures have highlighted that the expression change of lncRNAs has critical and clinically predictive roles in tumorigenesis (Elchuri et al, 2018). More and more lncRNAs were repor- (Hu et al, 2018), MT1JP (Bi et al, 2018), LIN00152 (Li et al, 2018), CCAT1 (Zhang et al, 2017), BANCR (Su et al, 2015), H19 (Zhang et al, 2018a), BDNF-AS (Shang et al, 2018), MALAT1 (Liu et al, 2017) and HOTAIR (Dong et al, 2016).…”

pRB-Depleted Pluripotent Stem Cell Retinal Organoids Recapitulate Cell State Transitions of Retinoblastoma Development and Suggest an Important Role for pRB in Retinal Cell Differentiation

“…Advances in next generation sequencing are enabling detailed expression and epigenetic studies of tumors, providing molecular insights at the single-cell level. Our group 49 and others 43 , 51 , 61 are utilizing these tools to understand the composition of Rb tumor tissues and to determine how pRB inactivation results in aberrant RNA processing events, genome instability and changes in metabolism and mitochondria biogenesis. These insights however focus on the end stage of tumor development, which precludes detailed insights into the transcriptional events of each state cell transition during Rb development.…”

Retinoblastoma and mosaic 13q deletion: a case report

“…Therefore, retinoblastoma presents a stable genome with few genetic events described and epigenetic deregulation appears to have a notable role [ 19 ]. Studies based on RNA-sequencing could continue to shed light on the genes and signaling pathways involved in retinoblastoma development [ 20 ]. In regards to common mutated genes in retinoblastoma, we determined BCOR and CREBPP status without detecting pathogenic variants.…”