CALR gene mutational profile in myeloproliferative neoplasms with non-mutated JAK2 in Moroccan patients: A case series and germline in-frame deletion

Curr Res Transl Med. Jan-Mar 2017;65(1):15-19. doi: 10.1016/j.retram.2016.08.002. Epub 2016 Nov 3.

Abstract

Background: The discovery of somatic mutations within the gene encoding calreticulin (CALR) in 2013 represented a major milestone in the molecular diagnosis of BCR-ABL negative myeloproliferative neoplasms (MPN). In fact, exome sequencing revealed that most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) lacking JAK2 or MPL mutations, harbor somatic insertion and/or deletion in exon 9 of CALR gene. In this study, we identified the first CALR gene mutational landscape in Moroccan patients with MPN nonmutated for the JAK2 gene.

Methods: We performed Sanger sequencing of exon 9 of CALR gene in blood samples obtained from 33 Moroccan patients with ET or PMF non-mutated for JAK2.

Results: Of the 33 patients analyzed, we detected eight distinct variants in 15 patients (45.4%); six indel mutations, five with type 1 recurrent 52bp deletion, four with type 2 recurrent 5bp insertion and one in frame deletion which was found to be a germline variant suggesting a very rare condition in MPN.

Conclusion: This is the first cohort reported in CALR gene mutation analysis in Morocco. Our results were concordant with studies reported up to date and very encouraging in promoting the molecular diagnosis of myeloproliferative neoplasms in Moroccan patients. Moreover, the presence of a germline in frame deletion in a symptomatic patient should undermine the effectiveness of sizing assays without DNA sequencing in the diagnosis of CALR mutations.

Keywords: CALR; In frame deletion; Morocco; Myeloproliferative neoplasms.

MeSH terms

  • Adult
  • Aged
  • Calreticulin / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Germ-Line Mutation*
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / genetics*
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Morocco / epidemiology
  • Myeloproliferative Disorders / epidemiology
  • Myeloproliferative Disorders / genetics*
  • Reading Frames / genetics
  • Sequence Deletion*

Substances

  • CALR protein, human
  • Calreticulin
  • JAK2 protein, human
  • Janus Kinase 2