Identification of Novel Functional Variants of SIN3A and SRSF1 among Somatic Variants in Acute Myeloid Leukemia Patients
Jae-Woong Min1,7, Youngil Koh2,3,7, Dae-Yoon Kim3, Hyung-Lae Kim4, Jeong A Han5, Yu-Jin Jung6,
Sung-Soo Yoon2,3,*, and Sun Shim Choi1,*
1Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National
University, Chuncheon 24341, Korea, 2Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea,
3Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea, 4Department of Biochemistry,
School of Medicine, Ewha Woman’s University, Seoul 03760, Korea, 5Department of Biochemistry and Molecular Biology,
School of Medicine, Kangwon National University, Chuncheon 24341, Korea, 6Department of Biological Sciences, Kangwon
National University, Chuncheon 24341, Korea, 7These authors contributed equally to this work.
*Correspondence: (SSY); (SSC)
Received January 29, 2018; Revised February 25, 2018; Accepted March 8, 2018.; Published online May 15, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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The advent of massively parallel sequencing, also called nextgeneration sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AMLrelated genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as “hotzone” analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.
Keywords: acute myeloid leukemia, somatic variants, whole genome sequencing

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