Distribution of mutations according to diagnosis and description of the novel CALR mutation. (A) JAK2 mutations were present in 42 of 52 (80.8%) patients with PV, 40 of 55 (72.7%) patients with ET, and 12 of 20 (60%) patients with PMF. CALR mutations were identified in 6 of 55 (10.9%) patients with ET and 6 of 20 (30%) patients with PMF. The remaining 10 patients (19.2%) with PV, 9 patients (16.4%) with ET, and 2 patients (10%) with PMF did not carry any mutation. (B) The novel type 41 is a complex mutation, consisting of 2 separate deletion events of 1 bp and 7 bp. These 2 deletions were shown to be on the same allele by polymerase chain reaction product subcloning and sequencing, as described previously.9 The first deletion introduces a frameshift to alternative frame, which is common to all CALR exon 9 mutations, whereas the second deletion causes a frameshift to the third alternative frame at the end of exon 9. Because the next stop codon comes later in the third frame, this mutation creates the longest CALR protein described so far (20 amino acids longer than the wild type). Each vertical bar represents an amino acid: blue bars indicate negatively charged amino acids, red bars indicate positively charged amino acids, white bars indicate uncharged amino acids, and black bars indicate stop codons. Horizontal black bars below the frames denote the amino acid stretch encoded by the respective frame. The arrows indicate the location of the 2 deletions. 3′ UTR, 3′ untranslated region of the gene.
