Next-generation deep-sequencing detects multiple clones of CALR mutations in patients with BCR-ABL1 negative MPN

摘要

The identification of CALR (calreticulin) mutations in essentialthrombocythemia (ET) and primary myelofibrosis marked animportant step in identifying molecular lesions underlyingBCR-ABL1 negative myeloproliferative neoplasms (MPN).1,2 Exomesequencing has demonstrated that 146 of 151 patients with MPN(97%) have mutations in JAK2, MPL or CALR in a mutually exclusivemanner.2 However, little information is available thus far on lowlevel CALR mutations in these diseases, as the latter studies hadused less-sensitive Sanger sequencing or exome-based nextgeneration sequencing (NGS) technology. Here, we applied genescan analysis and amplicon-based deep-sequencing as previouslydescribed.3–5 We aimed at studying the occurrence of low-levelCALR mutations in BCR-ABL1 negative MPN and the comparabilityof these two methods.