Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic mastocytosis with eosinophilia and chronic myelomonocytic leukemia

• Published in: Blood cancer journal (New York) 2015-01, Vol.5 (1), p.e275-e275
• Main Authors: Lasho, T L, Finke, C M, Zblewski, D, Patnaik, M, Ketterling, R P, Chen, D, Hanson, C A, Tefferi, A, Pardanani, A
• Format: Article
• Language: English
• Subjects: 45/77; 692/699/1541/1990/2331; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Cancer Research; Eosinophilia - complications; Eosinophilia - genetics; Eosinophilia - pathology; Exome - genetics; Female; Hematology; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myelomonocytic, Chronic - complications; Leukemia, Myelomonocytic, Chronic - genetics; Leukemia, Myelomonocytic, Chronic - pathology; Male; Mastocytosis, Systemic - complications; Mastocytosis, Systemic - genetics; Mastocytosis, Systemic - pathology; Middle Aged; Mutation; Oncology; Original; original-article; Phosphotransferases (Alcohol Group Acceptor) - genetics
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2014.94

Although KIT D816V occurs universally in adult systemic mastocytosis (SM), the clinical heterogeneity of SM suggests presence of additional phenotype-patterning mutations. Because up to 25% of SM patients have KIT D816V-positive eosinophilia, we undertook whole-exome sequencing in a patient with aggressive SM with eosinophilia to identify novel genetic alterations. We conducted sequencing of purified eosinophils (clone/tumor sample), with T-lymphocytes as the matched control/non-tumor sample. In addition to KIT D816V, we identified a somatic missense mutation in ethanolamine kinase 1 ( ETNK1 N244S) that was not present in 50 healthy controls. Targeted resequencing of 290 patients showed ETNK1 mutations to be distributed as follows: (i) SM ( n =82; 6% mutated); (ii) chronic myelomonocytic leukemia (CMML; n =29; 14% mutated); (iii) idiopathic hypereosinophilia ( n =137;