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

A Tefferi, RL Levine, KH Lim, O Abdel-Wahab… - Leukemia, 2009 - nature.com
A Tefferi, RL Levine, KH Lim, O Abdel-Wahab, TL Lasho, J Patel, CM Finke, A Mullally, CY Li…
Leukemia, 2009nature.com
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%) …
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∼ 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.
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