Abstract 2487: Application of RegTools to TCGA samples for the identification of tumor-specific splice variants

Abstract

Abstract The interpretation of variants in cancer is frequently focused on direct protein coding alterations. However, this analysis strategy excludes somatic mutations in non-coding regions of the genome and even exonic mutations may have unidentified non-coding consequences. To address this issue, we created RegTools (Feng et al. 2018), a free, open-source software package that integrates analysis of somatic variant calls from genomic data with splice junctions extracted from transcriptomic data in order to efficiently identify variants that may cause aberrant splicing in tumors. Initially, this software was developed using 188 cancer samples from 4 cancer types and enabled us to identify important non-coding variants which would otherwise be undervalued or perhaps even completely ignored by traditional methods and annotators. Here, we present the application of RegTools to over 10,000 TCGA samples in an effort to identify somatic variants that are associated with alternative splicing patterns within these tumors. In order to perform this analysis, we obtained all tumor samples that had somatic variant VCF files and RNA-seq bam files from the Genomic Data Commons (GDC). Included within these samples are more than 700 solid tissue normal samples, which will be used as a panel of normals in order to filter out variants and splicing events that are not tumor specific. We plan to present on the significance of our findings when analyzing these samples within their respective tumor type and across all tumor types. We also plan to present on whether these aberrant splicing events that result from somatic mutations might interfere with predicted neoantigens pVAC-Seq (Hundal et al. 2016). RegTools is freely available and open source (www.regtools.org). Citation Format: Kelsy C. Cotto, Yang-Yang Feng, Zachary L. Skidmore, Obi L. Griffith, Malachi Griffith. Application of RegTools to TCGA samples for the identification of tumor-specific splice variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2487.