title: The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts.
abstract: BACKGROUND
  Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting.
  
  
  METHODS
  We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2).
  
  
  RESULTS
  The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083).
  
  
  CONCLUSIONS
  Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS.
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. kmg1970@hanmail.net.
authors.forename: Min-Gu
authors.initials: MG
authors.lastname: Kang
authors.affiliation: College of Korean Medicine, Dongshin University, 185 Gunjaero, Naju, Jeollanam-do, 520-714, South Korea. 98lani@gmail.com.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. sbym12@naver.com.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Seo
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. hermes2014@gmail.com.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju, South Korea. zebrafish@chonnam.ac.kr.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. alpinboy@hanmail.net.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. shinjh@chonnam.ac.kr.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. spsuh@chonnam.ac.kr.
authors.forename: Soon-Pal
authors.initials: SP
authors.lastname: Suh
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. f0115@jnu.ac.kr.
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. mgshin@chonnam.ac.kr.|Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju, South Korea. mgshin@chonnam.ac.kr.|Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea. mgshin@chonnam.ac.kr.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000235:genetics*; D000072668:Splicing Factor U2AF
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors