title: Detection of mutations in JAK2 exons 12-15 by Sanger sequencing.
abstract: BACKGROUND
  The Janus kinase (JAK)2 p.V617F gain-of-function mutation is a hallmark of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). This study analyzed JAK2 mutations in 1811 patients tested between 2010 and 2013.
  
  
  METHODS
  Exons 12-15 of JAK2 were sequenced in 1706 samples, and patients harboring mutations were clinically evaluated.
  
  
  RESULTS
  Of 271 patients (16%) with JAK2 mutations, 148 (54.6%) were female and 123 (45.4%) were male; 103 (38%) were local and 168 (62%) were referred; and 13 (5%) had additional genetic abnormalities. The median patient age was 54 years, and there was only one pediatric patient. In agreement with previous reports, 262 patients (96.7%) were positive for the JAK2 p.V617F mutation. Non-p.V617F JAK2 mutations were detected in the remaining nine (3.3%) patients: five (1.8%) had a p.G571S mutation, and one (0.3%) each had p.E543_D544del, p.Y570Y silent, p.R541_E543delinsK, and p.I540_N542delinsM mutations. Diagnosis of 103 (38%) in-house cases revealed a predominance of MPN patients (87 cases, or 84.4%).
  
  
  CONCLUSIONS
  JAK2 p.V617F was the most prevalent mutation detected among patients in this study. Non-p.V617F JAK2 mutations were identified in exons 12 and 13 corresponding to recently reported mutations, except for the novel p.I540_N542delinsM.
authors.affiliation: Pathology Department, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors.forename: N
authors.initials: N
authors.lastname: Alghasham
authors.affiliation: Regional Lab and Blood Bank, King Saud Medical City, Riyadh, Saudi Arabia.
authors.forename: Y
authors.initials: Y
authors.lastname: Alnouri
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: H
authors.initials: H
authors.lastname: Abalkhail
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Khalil
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D003062:Codon; D005091:Exons; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D003062:Codon; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: JAK2 mutation; MPNs; essential thrombocythemia; polycythemia vera; primary myelofibrosis