TET2
In databases:
● Enzyme Number (IUBMB): EC 1.14.11.n2
Gene locus:
4q24
Protein name:
Tet (ten-eleven-translocation) oncogene family member 2
Protein Size:
2002 amino acids; about 224 kDa
Function:
The TET proteins (TET1, TET2, TET3) are members of the 2-oxoglutarate (2-OG)- and Fe(II)-dependent dioxygenase that are able to convert 5-methyl-cytosine (5-mC) to 5-hydroxymethylcytosine (hmC). TET2 play an important role in the regulation of myelopoiesis.
Cancer-related alterations:
Somatic TET2 mutations are observed in up to 20% of tumors affecting haematopoietic and lymphoid tissues. There are no mutational hot spots. Deletions, insertions, point mutations are found.
TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis).
TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.
TET2 is frequently mutated in myelodysplastic syndromes, a heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. Myelodysplastic syndromes are considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML).
References (open access):
Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Schaub FX, Looser R, Li S, Hao-Shen H, Lehmann T, Tichelli A, Skoda RC. Blood. 2010 Mar 11;115(10):2003-7.
Molecular basis of myelodysplastic/myeloproliferative neoplasms. Reiter A, Invernizzi R, Cross NC, Cazzola M. Haematologica. 2009 Dec;94(12):1634-8.
TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Kosmider O, Gelsi-Boyer V, Ciudad M, Racoeur C, Jooste V, Vey N, Quesnel B, Fenaux P, Bastie JN, Beyne-Rauzy O, Stamatoulas A, Dreyfus F, Ifrah N, de Botton S, Vainchenker W, Bernard OA, Birnbaum D, Fontenay M, Solary E; Groupe Francophone des Myélodysplasies. Haematologica. 2009 Dec;94(12):1676-81.
Mutation in TET2 in myeloid cancers. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lécluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguié F, Fontenay M, Vainchenker W, Bernard OA. N Engl J Med. 2009 May 28;360(22):2289-301.
Aucun commentaire:
Enregistrer un commentaire