Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates

A. Tefferi, R. L. Levine, K. H. Lim, O. Abdel-Wahab, T. L. Lasho, J. Patel, C. M. Finke, A. Mullally, C. Y. Li, A. Pardanani, D. G. Gilliland

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173 Scopus citations


TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene located at chromosome 4q24, and was recently reported to be mutated in ∼14% of patients with JAK2V617F-positive myeloproliferative neoplasms. We used high-throughput DNA sequence analysis to screen for TET2 mutations in bone marrow-derived DNA from 48 patients with systemic mastocytosis (SM), including 42 who met the 2008 WHO (World Health Organization) diagnostic criteria for SM and 6 with FIP1L1-PDGFRA. Twelve (29%) SM, but no FIP1L1-PDGFRA patients, had TET2 mutations. A total of 17 mutations (13 frameshift, 2 nonsense and 2 missense) were documented in 2 (15%) of 13 indolent SM patients, 2 (40%) of 5 aggressive SM, and 8 (35%) of 23 SM associated with a clonal non-mast cell-lineage hematopoietic disease (P = 0.52). KITD816V was detected by PCR sequencing in 50 or 20% of patients with or without TET2 mutation (P = 0.05), respectively. Multivariable analysis showed a significant association between the presence of TET2 mutation and monocytosis (P = 0.0003) or female sex (P = 0.05). The association with monocytosis was also observed in non-indolent SM (n = 29), in which the presence of mutant TET2 did not affect survival (P = 0.98). We conclude that TET2 mutations are frequent in SM, segregate with KITD816V and influence phenotype without necessarily altering prognosis.

Original languageEnglish (US)
Pages (from-to)900-904
Number of pages5
Issue number5
StatePublished - Jan 1 2009


ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Tefferi, A., Levine, R. L., Lim, K. H., Abdel-Wahab, O., Lasho, T. L., Patel, J., Finke, C. M., Mullally, A., Li, C. Y., Pardanani, A., & Gilliland, D. G. (2009). Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia, 23(5), 900-904.