Identification of Novel Functional Variants of SIN3A and SRSF1 among Somatic Variants in Acute Myeloid Leukemia Patients
- 주제(키워드) acute myeloid leukemia , somatic variants , whole genome sequencing
- 주제(기타) Biochemistry & Molecular Biology; Cell Biology
- 설명문(일반) [Min, Jae-Woong; Choi, Sun Shim] Kangwon Natl Univ, Inst Biosci & Biotechnol, Coll Biomed Sci, Div Biomed Convergence, Chunchon 24341, South Korea; [Koh, Youngil; Yoon, Sung-Soo] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 03080, South Korea; [Koh, Youngil; Kim, Dae-Yoon; Yoon, Sung-Soo] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 03080, South Korea; [Kim, Hyung-Lae] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul 03760, South Korea; [Han, Jeong A.] Kangwon Natl Univ, Sch Med, Dept Biochem & Mol Biol, Chunchon 24341, South Korea; [Jung, Yu-Jin] Kangwon Natl Univ, Dept Biol Sci, Chunchon 24341, South Korea
- 발행기관 KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151415
- 본문언어 영어
- Published As http://dx.doi.org/10.14348/molcells.2018.0051
초록/요약
The advent of massively parallel sequencing, also called next-generation 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) AML-related 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.
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