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Correspondence
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. 1Cancer Molecular Diagnostics, St. James Hospital, Dublin, Ireland
  2. 2Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK
  3. 3Department of Haematology, Tallaght Hospital, Dublin, Ireland
  4. 4Department 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}stjames.ie

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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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