Detection of mutations in JAK2 exons 12-15 by Sanger sequencing

Int J Lab Hematol. 2016 Feb;38(1):34-41. doi: 10.1111/ijlh.12425. Epub 2015 Sep 11.

Abstract

Introduction: 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%).

Conclusion: 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.

Keywords: JAK2 mutation; MPNs; essential thrombocythemia; polycythemia vera; primary myelofibrosis.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Codon
  • Exons*
  • Female
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Phenotype
  • Sequence Analysis, DNA / methods

Substances

  • Codon
  • JAK2 protein, human
  • Janus Kinase 2

Associated data

  • GENBANK/NM004972
  • GENBANK/NM_004972.3