Frequent TET2 mutations in systemic mastocytosis

Clinical, KITD816V and FIP1L1-PDGFRA correlates

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)900-904
Number of pages5
JournalLeukemia
Volume23
Issue number5
DOIs
StatePublished - 2009

Fingerprint

Systemic Mastocytosis
Mutation
Frameshift Mutation
Cell Lineage
Tumor Suppressor Genes
DNA Sequence Analysis
Oncogenes
Chromosomes
Bone Marrow
Phenotype
Polymerase Chain Reaction
Survival

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Tefferi, A., Levine, R. L., Lim, K. H., Abdel-Wahab, O., Lasho, T. L., Patel, J., ... Gilliland, D. G. (2009). Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia, 23(5), 900-904. https://doi.org/10.1038/leu.2009.37

Frequent TET2 mutations in systemic mastocytosis : Clinical, KITD816V and FIP1L1-PDGFRA correlates. / Tefferi, Ayalew; Levine, R. L.; Lim, K. H.; Abdel-Wahab, O.; Lasho, T. L.; Patel, J.; Finke, C. M.; Mullally, A.; Li, C. Y.; Pardanani, Animesh D; Gilliland, D. G.

In: Leukemia, Vol. 23, No. 5, 2009, p. 900-904.

Research output: Contribution to journalArticle

Tefferi, A, Levine, RL, Lim, KH, Abdel-Wahab, O, Lasho, TL, Patel, J, Finke, CM, Mullally, A, Li, CY, Pardanani, AD & Gilliland, DG 2009, 'Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates', Leukemia, vol. 23, no. 5, pp. 900-904. https://doi.org/10.1038/leu.2009.37
Tefferi, Ayalew ; Levine, R. L. ; Lim, K. H. ; Abdel-Wahab, O. ; Lasho, T. L. ; Patel, J. ; Finke, C. M. ; Mullally, A. ; Li, C. Y. ; Pardanani, Animesh D ; Gilliland, D. G. / Frequent TET2 mutations in systemic mastocytosis : Clinical, KITD816V and FIP1L1-PDGFRA correlates. In: Leukemia. 2009 ; Vol. 23, No. 5. pp. 900-904.
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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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AU - Lim, K. H.

AU - Abdel-Wahab, O.

AU - Lasho, T. L.

AU - Patel, J.

AU - Finke, C. M.

AU - Mullally, A.

AU - Li, C. Y.

AU - Pardanani, Animesh D

AU - Gilliland, D. G.

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