title: Highly variable mutational profile of ASXL1 in myelofibrosis.
abstract: OBJECTIVE
  Somatic mutations in ASXL1 seem to have a negative prognostic impact in patients with several myeloid neoplasms, including myelofibrosis (MF). The aim of this work was to determine the prevalence and profile of ASXL1 mutations in MF.
  
  
  METHODS
  We analyzed mutations in ASXL1 in 70 consecutive MF patients from 8 Spanish hospitals by means of Sanger sequencing, as well as JAK2, CALR, and MPL mutations.
  
  
  RESULTS
  ASXL1 mutations were found in 16/70 (23%) of cases, most commonly p.Gly646TrpfsX12 (5/16). Most mutations (13/16) were frameshift mutations. Of 54 ASXL1- wild-type patients, 32 (59%) had at least one single nucleotide polymorphism (SNP), 27 of them had g.78128C>T, g.79017A>C, and g.79085T>C [triple SNP (TSNP) patients]. The 5-yr overall survival probability of TSNP patients was 67% (95% CI, 43-91%) vs. 90% (95% CI, 77-100%) in ASXL1-WT patients (P = 0.152).
  
  
  CONCLUSIONS
  ASXL1 mutations were found in 23% of cases, p.Gly646TrpfsX12 being the most frequent. About 85% of mutations were found only in individual cases and 46% had not previously been reported, a pattern also seen in other series. Fifty percent of ASXL1-WT patients had a combination of three specific SNPs that might have a prognostic correlation that needs to be determined in larger series.
authors.affiliation: Department of Hematology, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain. 48096mst@comb.cat.
authors.forename: Marc
authors.initials: M
authors.lastname: Sorigué
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Josep-Maria
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: García
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cabezón
authors.affiliation: ICO-Hospital Duran i Reynals, Hospitalet del Llobregat, Catalonia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vélez
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marcé
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Xicoy
authors.affiliation: ICO-Hospital Josep Trueta, Girona, Spain.
authors.forename: Cristalina
authors.initials: C
authors.lastname: Fernández
authors.affiliation: Hospital Sant Jaume de Calella, Girona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Buch
authors.affiliation: Hospital de Granollers, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cortes
authors.affiliation: Hospital de Mataró, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Plensa
authors.affiliation: ICO-Hospital Josep Trueta, Girona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
authors.affiliation: ICO-Hospital Duran i Reynals, Hospitalet del Llobregat, Catalonia, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Boqué
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Evarist
authors.initials: E
authors.lastname: Feliu
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Zamora
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D012097:Repressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D012097:Repressor Proteins; D053614:Janus Kinase 2
keywords: ASXL1; myelofibrosis; single nucleotide polymorphism