Streamlined Analysis And Interpretation Of Rna Editing Variants From Melanoma Cancer Samples

Of special interest in a clinical setting is the identification and interpretation of somatic variants from the DNA of a tumor/normal matched pair. Studies have shown that a large proportion of variants present in DNA are not present in the RNA and vice versa due to RNA-Editing and other unknown molecular processes1. In addition, recent publications show that RNA-editing plays an important role in cancer2,3. These findings can have strong implications for clinical diagnostics where the correct identification and interpretation of somatic variants from tumor/normal matched samples is essential. We took a published Whole Trancriptome/Whole Exome Sequencing dataset of tumor and peripheral blood from two patients with uveal melanomas5. We looked for somatic variants present in the RNA, but absent in the DNA using CLC Cancer Research Workbench. A strong mutation signature for C-T, A-G changes was found, which result from Adenosine to Inosine changes, a typical RNA-Editing event, which was recently published to be common in human and is mediated by ADAR proteins. By running Ingenuity Variant Analysis directly from CLC Cancer Research Workbench we found RNA-Editing found in these two patients is highly associated with cancer and more specifically with Melanoma directly. Some of the variants directly associated with Melanoma were classified as likely pathogenic and were not described in COSMIC, but present in Ingenuity9s large Knowledge Base. 1) Widespread RNA and DNA Sequence Differences in the Human Transcriptome. Mingyao Li, Isabel X. Wang, Yun Li, Alan Bruzel, Allison L. Richards, Jonathan M. Toung, and Vivian G. Cheung. Science 1 July 2011: 333 (6038), 53-58. 2) RNA editing in RHOQ promotes invasion potential in colorectal cancer. Sae-Won Han et al. J Exp Med 2014 211:613-621. 3) A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Tim Hon Man Chan et al.Gut 2014;63:5 832-843 4) A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes.Genome Res. March 2014 24: 365-376 5) Harbour JW et al., “Frequent mutation of BAP1 in metastasizing uveal melanomas.”, Science, 2010 Nov 4;330(6009) Citation Format: Anika Joecker, Rupert Yip, Anne Arens, Bodil Oester, Douglas Basset, Bryant Macy. Streamlined analysis and interpretation of RNA editing variants from melanoma cancer samples. [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 1925. doi:10.1158/1538-7445.AM2015-1925