Abstract 59: Identification of RNA editing events in cancer using high-throughput sequencing data

Abstract

Abstract RNA editing is a post-transcriptional modification of pre-mRNA that has recently been identified as an additional epigenetic mechanism relevant to cancer development and progression. With projects like The Cancer Genome Atlas (TCGA) providing high-throughput sequencing datasets measuring both DNA and RNA from the same patients across multiple cancers, it is now possible to search for RNA editing events at a genome-wide scale. Using fully-sequenced tumor and matched-normal genomes and RNA-Seq data from TCGA project, we will identify RNA editing events in acute myeloid leukemia (AML) patients. We have analyzed the tumor and matched normal genomes to identify SNPs, mutations (both germline and somatic), and heterozygosity across the entire genome. By comparing the patient's genomic data to the RNA transcripts assembled by the UCSC RNA-Seq pipeline, we can identify any bases that were transcribed abnormally. All putative RNA editing events will be assessed according to the most common types of RNA editing, such as the deamination of adenosine into inosine (A-to-I) or the conversion of cytosine into uracil (C-to-U). Local phasing information inferred from the genomic sequence will be used to disambiguate potential RNA editing events found at heterozygous locations. As a positive control, we will confirm RNA-editing events previously discovered experimentally in AML patients, such as an A-to-I conversion in the protein tyrosine phosphatase PTPN6 gene. The PTPN6 gene is recognized as a tumor suppressor gene and is important for the down-regulation of growth-promoting receptors. The A-to-I conversion of adenosine 7866 causes the splicing mechanism to ignore a splicing junction, leading to a non-functional PTPN6 protein via the inclusion of an intron in the mature RNA transcript. Using the TCGA sequencing data, we will identify all AML samples that exhibit this particular A-to-I conversion as well as the inclusion of the intron with the RNA-Seq data. In addition, we will report novel RNA editing events in AML and other cancer types and look for patterns that may be cancer specific or globally relevant to cancer development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 59. doi:10.1158/1538-7445.AM2011-59