Abstract 2515: Understanding metabolic dysfunction in retinoblastoma development

Metabolic dysfunction or reprogramming is the underlying cause of many diseases including cancer. In this study, we looked into the transcriptomic and metabolomic profile of retinoblastoma (Rb), a pediatric eye cancer, from tumor and normal tissue, aqueous humor, vitreous humor and tear. The samples were collected from enucleated eyes of 9 subjects and 2 deceased controls, whose cause of death is not due to any eye related disease. The study was corroborated with cell line models of retinoblastoma, used for metabolic phenotyping. Combined pathway analysis of transcriptomics data from subject tissue samples and retinoblastoma cell line WERI-Rb-1 revealed a significant overlap in the differentially regulated genes belonging to both glycolysis and OXPHOS pathways. The results were correlated with Rb1 overexpressed and its respective control also. To better understand the implications of these two major pathways in the progression of retinoblastoma, metabolic study using Seahorse analyzer enables measurement of extracellular flux (oxygen consumption rate and extracellular acidification rate) to provide insight into mitochondrial function and glycolytic activity. Using a pharmacological approach, the contribution of glucose, glutamine and fatty acid oxidation pathways can be assessed. Overall the study demonstrates the value of using a multi-omics approach with functional metabolic profiling to understand the extent of metabolic dysfunction in retinoblastoma and also to identify implications of various biological pathways in Rb. Citation Format: Nilanjan Guha, Carolina Livi, Vishnu Suresh Babu, Lisa Winer, Deepak SA, Syed Lateef, Seetaraman Gundimeda, Arunkumar Padmanabhan, Brian Dranka, Arkasubhra Ghosh. Understanding metabolic dysfunction in retinoblastoma development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2515. doi:10.1158/1538-7445.AM2017-2515