CALR Mutation Analysis
Calreticulin is a functionally complex Ca2+ binding protein localized primarily in the endoplasmic reticulum (ER) but is also found in the nucleus, cell membranes and extracellular matrix. Calreticulin protein consists of three domains: amino terminal N-domain (residues 1 to 180), central proline-rich P-domain (residues 181 to 290) and carboxyl terminal C-domain (residues 291 to 400). Functionally, calreticulin is believed to participate in Ca2+homeostasis, handling of misfolded proteins, cell adhesion, immune response to caner, phagocytosis and signaling. Abnormal expression of Calreticulin has been described in various cancers.
Novel CARL mutations (exon 9 deletions and insertions) have been found in JAK2 or MPL unmutated primary myelofibrosis (PMF) and essential thrombocythemia (ET). CALR mutations are mutually exclusive of JAK2 or MPL mutations. In ET, CALR, compared to JAK2, mutations are associated with lower hemoglobin level, lower leukocyte count, higher platelet count, lower risk of thrombosis and better survival. In PMF, the association is with lower leukocyte count, higher platelet count and better survival.
Fluorescence-based PCR and capillary electrophoresis of DNA is performed to screen for insertions and deletions in exon 9 of CALR. PCR-based Sanger sequencing will be used to define mutations detected by capillary electrophoresis screening and sequence codons 351 to 404 in exon 9 of CALR. For diagnostic samples with mutation, PCR-based Sanger sequencing will subsequently be utilized to define mutations detected by capillary electrophoresis screening. For follow-up samples capillary electrophoresis-based assay will be performed to monitor the mutation detected at diagnosis.
This assay will detect insertion and deletion mutations present in codons 351 through 404 of CALR. The sensitivity of the capillary electrophoresis assay is 2.5% of variant sequence in the background of wild-type sequence and the Sanger sequencing assay is 5% variant sequence in the background of wild-type sequence.
10 mL peripheral blood, 2-5mL bone marrow aspirate.
Please provide a copy of the corresponding pathology report.
Additional charges may apply for tissue extraction.
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