title: [Mutational analysis of RNA splicing machinery genes SF3B1, U2AF1 and SRSF2 in 118 patients with myelodysplastic syndromes and related diseases].
abstract: Objective:To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases.Methods:Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis.Results:Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) yearsvs51 (13-84) years,z=-1.981,P=0.048], lower HGB level[63 (40-95) g/Lvs77 (34-144) g/L,z=-3.192,P=0.001], higher platelet counts[121 (22-888) ×10(9)/Lvs59 (6-1 561) ×10(9)/L,z=-3.305,P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122)vs0.017 (0-0.268) ,z=-2.885,P=0.004], higher ring sideroblasts percent [0 (0-64%)vs0 (0-58%) ,z=-4.664,P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients.Conclusion:Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.
authors.affiliation: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: Y N
authors.initials: YN
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: F M
authors.initials: FM
authors.lastname: Gui
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: Q H
authors.initials: QH
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes; D010750:Phosphoproteins; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF; D055815:Young Adult
chemical_list: D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors
keywords: DNA mutational analysis; Gene, SF3B1; Gene, SRSF2; Gene, U2AF1; Myelodysplastic syndromes