Abstract 2178: Comparison and interpretation of variants in RNA and DNA from sarcoma cancer sample

Identification and interpretation of somatic variants using DNA from matched tumor/normal pairs is crucial for understanding the mechanisms behind cancer. Studies have shown that a large proportion of variants present in the DNA are not present in the RNA and vice versa due to RNA-editing and other unknown molecular processes. In addition, recent publications show that RNA-editing plays an important role in cancer. These findings can have strong implications for clinical diagnostics where correct identification and interpretation of somatic variants from matched tumor/normal samples is essential. In this study we will investigate somatic variants that are only present in the DNA or the RNA of pleomorphic undifferentiated sarcoma. For this approach we will first identify somatic variants in the DNA using Exome Sequencing data and in the RNA using RNA-Seq data from a matched tumor/normal pair. Somatic variants in DNA as well as RNA are then again filtered for germline variants using the DNA of the normal sample and the RNA of the normal sample. Somatic variants found in only DNA or only RNA are further investigated using Ingenuity's large Knowledge Base as well as HGMD and PGMD. We will show which class of proteins is mainly affected by the RNA editing events and which pathways are mainly affected. We will also highlight implications for clinical diagnostics using DNA only. The complete analysis will be done using the new integrated QIAGEN tool suite of CLC Cancer Research Workbench, Ingenuity Variant Analysis and Biobase Genome Trax. Citation Format: Bodil Øster, Anika Joecker, Rupert Yip, Frank Schacherer, Douglas Basset, Donald Salter, Richard L. Hayward, Ted R. Hupp. Comparison and interpretation of variants in RNA and DNA from sarcoma cancer sample. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2178. doi:10.1158/1538-7445.AM2015-2178