Detection of low allele burden of JAK2 exon 12 mutations using TA-cloning in patients with erythrocytosis

Jpn J Clin Oncol. 2009 Aug;39(8):509-13. doi: 10.1093/jjco/hyp048. Epub 2009 Jun 2.

Abstract

Objective: Polycythemia vera (PV) is a clonal myeloproliferative neoplasia associated with the activation of the Janus-activating kinase 2 (JAK2) mutation. The aim of this study is to identify clonal expansion of exon 12 mutations.

Methods: We performed DNA sequencing of the JAK2 exon 12 after TA-cloning in JAK2-V617F-negative and JAK2-V617F-positive PV patients.

Results and conclusions: We found clonal mutations (i.e. H538-K539delinsL and D544G) in 3 of 7 JAK2-V617F-negative PV patients, however, unlike JAK2-V617F, allele burden of JAK2 exon 12 mutation was low. Since allele-specific PCR is able to amplify only the limited region which contains known mutations with gain-of-function, we need to clarify the biological implications of unknown single nucleotide substitution of the JAK2 exon 12 with low clonal burden in erythrocytosis patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Exons / genetics*
  • Female
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Polycythemia / genetics*
  • Polycythemia / pathology
  • Polycythemia Vera / genetics*
  • Polycythemia Vera / pathology
  • Prognosis
  • Survival Rate
  • Young Adult

Substances

  • JAK2 protein, human
  • Janus Kinase 2