Abstract B038: Accurate quantitative profiling of rna modifications and their associations with glioblastoma

Abstract

Abstract Every chemical group that is added to one of the canonical ribonucleotides, i.e., RNA modification, in a specific transcript can potentially alter the RNA folding as well as the RNA-protein interactions. Hence, RNA modifications are considered as post-transcriptional regulators for RNA splicing, RNA stability, and translation, just to name a few. Today, 170+ different RNA modifications have been identified, but only half a dozen of them are linked to glioblastoma (GBM). On the other hand, other RNA biology studies indicated the interplays between RNA modifications within a specific epitranscriptome could play a regulatory role in cellular activities. Although suitable methods for profiling RNA modifications in a specific epitranscriptome are available, the lack of ribonucleoside standards has prohibited the accurate quantification of each detectable RNA modification. To address this analytical challenge, our group has recently developed a mass spectrometric method that can achieve accurate quantitative profiling of untargeted RNA modifications without using any standards. Using the developed method, all the RNA modifications in patient-derived GBM cell lines could be profiled with high accuracy. In total, 31 different RNA modifications were detected in the GBM epitranscriptomes. By comparing with the profile detected in healthy human brain tissues, a unique set of upregulated RNA modifications is associated with the development of GBM. These findings are supported by the upregulated gene expression data obtained from GBM patients that are available in The Cancer Genome Atlas program. Citation Format: Frank A Morales Shnaider, Coston Eddings, Jennifer Simpson, Bakhos A. Tannous, Norman Chiu. Accurate quantitative profiling of rna modifications and their associations with glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B038.