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Updated: Jun 25, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates
A Tefferi1, R L Levine, K-H Lim
1Divisions of Hematology and Hematopathology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
Abstract:
TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene located at chromosome 4q24, and was recently reported to be mutated in approximately 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.
Insights
TET2 mutations are common in systemic mastocytosis (SM), often co-occurring with KITD816V. These TET2 mutations influence disease characteristics like monocytosis but do not appear to impact patient survival.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene.
- TET2 mutations have been reported in myeloproliferative neoplasms.
- Systemic mastocytosis (SM) is a myeloproliferative neoplasm.
Purpose of the Study:
- To investigate the frequency and impact of TET2 mutations in systemic mastocytosis (SM).
- To determine the association of TET2 mutations with clinical features and prognosis in SM.
Main Methods:
- High-throughput DNA sequencing was used to screen for TET2 mutations in bone marrow DNA from 48 SM patients.
- KITD816V mutation status was assessed by PCR sequencing.
- Multivariable analysis was employed to evaluate associations between TET2 mutations and clinical parameters.
Main Results:
- TET2 mutations were identified in 29% of SM patients, but not in FIP1L1-PDGFRA patients.
- Mutations were found in 15% of indolent SM, 40% of aggressive SM, and 35% of SM associated with other myeloid diseases.
- TET2 mutation presence was significantly associated with monocytosis and female sex, and segregated with KITD816V.
- TET2 mutations did not affect survival in non-indolent SM.
Conclusions:
- TET2 mutations are frequent in systemic mastocytosis.
- TET2 mutations influence SM phenotype, particularly monocytosis, and are associated with KITD816V.
- Despite influencing phenotype, TET2 mutations do not appear to alter the prognosis of SM.
