A novel type of +2‐base pair frameshift CALR mutation in a patient with myeloproliferative neoplasm. (12th June 2018)

• Record Type: Journal Article
• Authors: Kim, Hyun‐Young; Kim, Jong‐Won; Kim, Sun‐Hee; Chang, Myung Hee; Kim, Hee‐Jin
• Is Part Of: European journal of haematology. Volume 101:Number 2(2018)
• Page Start: 216
• Page End: 219
• Publication Date: 2018-06-12
• Subjects: +2‐base pair frameshift -- CALR mutation -- double mutations -- myeloproliferative neoplasm; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13076
• Languages: English
• ISSNs: 0902-4441

Abstract

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.