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False-negative CALR mutation in a suspected myeloproliferative neoplasm: identification, resolution and corrective action
  1. Karl Haslam1,
  2. Sarah Dell2,
  3. Emer Atkinson1,
  4. Helen Enright3,
  5. Patrick Thornton4,
  6. Stephen E Langabeer1
  1. 1 Cancer Molecular Diagnostics, St. James Hospital, Dublin, Ireland
  2. 2 Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK
  3. 3 Department of Haematology, Tallaght Hospital, Dublin, Ireland
  4. 4 Department of Haematology, Beaumont Hospital, Dublin, Ireland
  1. Correspondence to Dr Stephen E Langabeer, Cancer Molecular Diagnostics, Central Pathology Laboratory, St. James’s Hospital, Dublin D08 E9P6, Ireland; slangabeer{at}

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Detection of insertion and/or deletion (indel) mutations in CALR exon 9, the gene that encodes the endoplasmic reticulum-associated, calcium binding protein calreticulin, is now considered a major criterion for the diagnosis of the myeloproliferative neoplasms (MPN) essential thrombocythaemia (ET) and primary myelofibrosis. MPN-associated CALR indel mutations all result in a +1 frame shift of the coding sequence, leading to an altered amino acid composition of the translated protein and loss of the endoplasmic reticulum retention motif. The two most common CALR mutations are a 52 bp deletion and a 5 bp insertion that account for >85% of indels; however, many others of varying size have been described at a much lower frequency.1 2 A number of screening methodologies can be employed to detect CALR mutations including Sanger sequencing, fluorescent PCR followed with fragment length analysis (FLA) by capillary electrophoresis, high-resolution melt curve analysis, next-generation sequencing and quantitative PCR: each approach having its own limits of …

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  • Handling editor Mary Frances McMullin.

  • Contributors KH, SD, EM and SEL performed laboratory studies. HE and PT provided patient care. All authors contributed to manuscript preparation and approved the submitted version.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.