WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
TET2
  • Information
  • View History
  • Pending Review
Interpretation 23
Tier 2
TET2
Variants
TET2 any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Myeloproliferative Neoplasm
Mast Cell Neoplasm
Acute Myeloid Leukemia
Primary Myelofibrosis
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

Ten-Eleven Translocation-2 (TET2) encodes a dioxygenase that converts 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC) and promotes DNA demethylation. TET2 is a tumor suppressor gene and loss-of-function via mutations, deletion and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutations is a common event in myeloid and lymphoid malignancies. TET2 is also present in about 10% of otherwise healthy elderly individuals with clonal hematopoiesis of indeterminate potential (CHIP) and in some patients with unexplained cytopenia but who do not satisfy diagnostic criteria for MDS, so-called clonal cytopenia with undetermined significance (CCUS). Mutations in TET2 occur in 50-60% of chronic myelomonocytic leukemias. Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. TET2 mutations are also found in 20-40% of systemic mastocytosis, 36% of blastic plasamcytoid dendritic cell neoplasm, 12-32% of acute myeloid leukemia, 10-20% of primary myelofibrosis, 10-33% of myelodysplastic syndromes, 10% of myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), 22% of polycythemia vera, and 16% of essential thrombocythemia. TET2 mutations are absent in juvenile myelomonocytic leukemia and show a low prevalence (less than 5%) in pediatric AML. Among lymphoid neoplasms, TET2 mutations are reported in approximately 30% of angioimmunoblastic lymphomas and less than 15 % of other mature T cell lymphomas and mature B cell lymphomas. In general, the mutations in TET2 are typically loss of function variants (frameshift, missense, nonsense mutations) that may be monoallelic or biallelic and occur throughout the gene. TET2 mutations tend to be mutually exclusive of mutations in IDH1/IDH2. TET2 mutations are associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome (PMID: 25092778). In acute myeloid leukemia with wild-type FLT3-ITD and normal karyotype or intermediate-risk cytogenetic abnormalities, TET2 mutations are associated with an unfavorable prognosis.

Citations
  1. Tefferi A, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 2009;23(5):900-4
  2. Tefferi A, et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia 2009;23(7):1343-5
  3. Kosmider O, et al. TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica 2009;94(12):1676-81
  4. Delhommeau F, et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360(22):2289-301
  5. Solary E, et al. The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. Leukemia 2014;28(3):485-96
  6. Elena C, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood 2016;128(10):1408-17
  7. Menezes J, et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 2014;28(4):823-9
  8. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  9. Pardanani A, et al. Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival. Am J Hematol 2016;91(9):888-93
  10. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  11. Vannucchi AM, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013;27(9):1861-9
  12. Patnaik MM, et al. Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) and the role of next-generation sequencing. Am J Hematol 2016;91(5):492-8
  13. Tefferi A, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv 2016;1(1):21-30
  14. Bejar R, et al. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol 2014;32(25):2691-8
  15. Malcovati L, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood 2014;124(9):1513-21
  16. Patel JP, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366(12):1079-89
Last updated: 2019-08-28 14:54:00 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use