Performance evaluation of fragment analysis for detecting <i>CALR</i> mutations and assessing variant allele frequency

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  • NEGISHI Tatsuya
    Department of Laboratory Medicine, Shinshu University Hospital
  • SHIGETO Shohei
    Department of Laboratory Medicine, Shinshu University Hospital
  • MATSUDA Kazuyuki
    Department of Health and Medical Sciences, Graduate School of Medicine, Shinshu University
  • MIYAZAKI Akari
    Department of Laboratory Medicine, Shinshu University Hospital
  • KONNO Saori
    Department of Laboratory Medicine, Shinshu University Hospital
  • NISHINA Sayaka
    Department of Hematology and Medical Oncology, Shinshu University School of Medicine
  • NAKAZAWA Hideyuki
    Department of Hematology and Medical Oncology, Shinshu University School of Medicine
  • UEHARA Takeshi
    Department of Laboratory Medicine, Shinshu University Hospital

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Other Title
  • フラグメント解析による<i>CALR</i>遺伝子変異検出の性能評価と変異アリル頻度測定に関する検討
  • フラグメント解析によるCALR遺伝子変異検出の性能評価と変異アリル頻度測定に関する検討
  • フラグメント カイセキ ニ ヨル CALR イデンシ ヘンイ ケンシュツ ノ セイノウ ヒョウカ ト ヘンイ アリル ヒンド ソクテイ ニ カンスル ケントウ

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Abstract

<p>Calreticulin (CALR) is the second most mutated gene, after Janus kinase 2 (JAK2) V617F, in essential thrombocythemia and primary myelofibrosis. The detection of CALR mutations is important for not only the diagnoses of these diseases but also the predictions of their respective prognoses. In this study, we evaluated the basic performance of fragment analysis for detecting CALR mutations and assessed the usefulness of variant allele frequency for the analysis. We found that the variant allele frequency of type2 mutations detected by fragment analysis was well correlated with the actual frequency, whereas that of type1 mutations was higher than the actual frequency. The limits of detection of type1 and type2 mutations by fragment analysis based on the variant allele frequency were 3% and 4%, respectively, which is sufficient for routine examination. Fragment analysis was used to analyze mutations in patients with essential thrombocythemia or primary myelofibrosis. Among 23 patients analyzed, 14 showed type1, four showed type2, and five showed other types of mutation. Fragment analysis can be successfully applied as a screening test because it can detect different types of CALR mutation, including minor mutations, with high sensitivity. Among the 13 patients with essential thrombocythemia showing type1 mutations, the variant allele frequency was found to be positively correlated with leucocyte and platelet counts and negatively correlated with hemoglobin concentration, thereby indicating that these data are affected by the variant allele frequency of CALR.</p>

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