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Eur J Haematol. 2018 Apr 4. doi: 10.1111/ejh.13076. [Epub ahead of print]

A novel type of +2-base pair frameshift CALR mutation in a patient with myeloproliferative neoplasm.

Author information

1
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
3
Division of Hematology-Oncology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.

Abstract

Somatic CALR mutations have been identified in the majority of JAK2 mutation-negative essential thrombocythaemia (ET) and primary myelofibrosis. Almost all CALR mutations have been reported to typically generate a +1-base pair (bp) frameshift in the open reading frame. Here, we describe an ET patient with a +2-bp frameshift CALR mutation. A 41-year-old man was admitted because of headache, and diagnosed as JAK2-negative ET. After 4 years, his disease progressed to post-ET myelofibrosis, and CALR mutation analysis demonstrated a +2-bp frameshift CALR mutation caused by two different CALR mutations, c.1139_1151del and c.1211_1215delinsTTGA, on the same allele. The resultant mutant protein sequence shared 19 amino acids with those from type 1 and type 2 CALR mutations, but the downstream C-terminal sequences were different. To our knowledge, CALR double mutations causing +2-bp frameshift are extremely rare. Identification of this novel type of CALR mutation has potential implications for better understanding of CALR oncogenesis.

KEYWORDS:

+2-base pair frameshift; CALR mutation; double mutations; myeloproliferative neoplasm

PMID:
29617043
DOI:
10.1111/ejh.13076

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