ClinVar

Klampfl et al. (2013) and Nangalia et al. (2013) identified a somatic 52-bp deletion in exon 9 of the CALR gene (1092_1143del) in patients with myeloproliferative neoplasms, including myelofibrosis (254450) and essential thrombocythemia (see 187950). CALR mutations and JAK2 and MPL mutations were mutually exclusive. The 52-bp mutation resulted in frameshift and premature termination (L367fsTer46). Klampfl et al. (2013) identified a total of 36 types of somatic insertion or deletion within exon 9 of CALR, all of which caused a frameshift to the same alternative reading frame and generated a novel C-terminal peptide in the mutant calreticulin. Klampfl et al. (2013) identified insertions or deletions in exon 9 of CALR in 88% of individuals with primary myelofibrosis with nonmutated JAK2 or MPL. The 52-bp deletion accounted for 53% of all cases of mutated CALR among several types of myeloproliferative neoplasm. Overexpression of this mutation resulted in cytokine-independent growth in vitro through the activation of STAT5 (601511). Nangalia et al. (2013) identified 23 patients with myelofibrosis who carried the L367fsTer46 mutation. Overall, Nangalia et al. (2013) identified 19 different somatic CALR mutations, all in exon 9 and all of which generated a +1 frameshift resulting in a mutant protein with a novel C terminal. CALR mutations were present in 18 of 32 patients (56%) with primary myelofibrosis and in 12 of 14 patients (86%) with progression of essential thrombocythemia to myelofibrosis. Neither Klampfl et al. (2013) nor Nangalia et al. (2013) detected CALR mutation in individuals with polycythemia vera.