Abstract A26: Analysis of Alternative Splicing Events in High- and Low-Grade Bladder Tumors

Abstract Functioning primarily in the rearrangement of identical pre-mRNA into different molecules, the alternative splicing (AS) contributes to the organism proteomic diversity. There are still unknown AS events, especially the aberrant splicing events that are associated to nonfunctional final products or tumorigenesis. For instance, hallmarks, such as apoptosis, metastasis, and angiogenesis, of certain types of cancer are known to be affected by some kind of aberrant splicing event. As examples, for BCLX gene, antiapoptotic and proapoptotic isoforms have been discovered, and, for the VEGFA gene, changes between proangiogenic and antiangiogenic isoforms expression have been detected in tumors and normal-matched samples, as well as among several distinct tissues. We hypothesize that AS events can also be associated and contribute to the origin and maintenance of specific tumor types and sub-types. We characterized the AS events in 35 samples of primary bladder tumors, classified as 20 high-grade (cells poorly differentiated, invasive and metastatic tumor), 11 low-grade (cell differentiated, noninvasive tumor), and 5 normal tissues. To access the AS events, we generated in total 2.5 billion of reads using RNAseq. The next step was mapping these reads against the human reference genome, using a set of in-house and publicly available pipelines to detect AS events in high-/low-grade bladder samples and normal tissues. As result, we observed 992 significant splicing events on high-grade tumors as compared to normal samples, 796 significant events on low-grade versus normal samples, and 871 significant events on low-grade versus high-grade tumors. After looking for some of these events in combinations of tumor grades and control, we found a tumor-specific isoform for RPS24 gene and five splicing events of genes RPL13A, RPL3, RPL37A, RPS27A, and RPL34 that are unique to high-grade tumors. We believe that these low-/high-grade AS specific events should be further studied in order to contribute to the understanding and to the development of new drugs for bladder tumors presenting low- or high-grade. Citation Format: André Luiz Ventura Sávio, Ricardo Piuco, Katia Ramos Moreira Leite, Daisy Maria Favero Salvadori, Pedro Alexandre Favoretto Galante, Luiz Otavio Ferraz Penalva. Analysis of alternative splicing events in high- and low-grade bladder tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A26.