title: Analysis of the Ten-Eleven Translocation 2 (TET2) gene mutation in myeloproliferative neoplasms.
abstract: Loss-of-function mutations in the putative tumor suppressor gene, Ten-Eleven Ttranslocation 2(TET2), have been identified recently in myeloproliferative neoplasms (MPNs). The present study analyzed the TET2 gene in 99 MPNs patients. The overall TET2 mutational frequency was 12.1% (22.2% in polycythemia vera (PV), 9.7% in essential thrombocythemia (ET), 18.2% in primary myelofibrosis (PMF,) and 0% in unclassified MPNs), and 11 mutations (p.Lys95Asnfs*18, p.Gln967Asnfs*40, p.Lys1022Glufs*4, p.Asp1314Metfs*49, p.Gln1534Alafs*43, p.Tyr1618Leufs*4, p.Leu1609Glufs*45, p.Gly1735*, Q599R, c.3409+1G>T, c.4044+2insT) were identified. All the patients with TET2 mutation were accompanied by the JAK2 V617F mutation. The existence of the TET2 mutation was not related to the patient's age, hematologic indices, JAK2 V617F allele burden, frequencies of organomegaly, marrow fibrosis, or thrombotic/hemorrhagic complications in entire MPN patients. However, tendencies toward higher JAK2 V617F allele burdens (88.0±4.3% vs. 19.1±28.7%, P=0.034) and higher Hct (47.4±5.4% vs. 25.5±6.2%, P=0.037) were detected in PMF patients harboring TET2 mutations. Moreover, a significantly higher frequency of organomegaly was identified in ET patients harboring the TET2 mutation (50% vs. 19.6%, P=0.018). The TET2 mutation most likely contributes to clinical phenotypes and shows a high accompanying rate with JAK2 V617F; larger scale studies involving more MPN patients are needed.
authors.affiliation: M.D.,Ph.D.; Department of Laboratory Medicine, Keimyung University School of Medicine, 56 Dalsung-ro, Jung-gu, Dongsan-dong, Daegu, Republic of Korea, 700-712; phone: 82 53 250 7266; fax: 82 53 250 7275; e-mail: ksksmom@dsmc.or.kr.
authors.forename: Jung-Sook
authors.initials: JS
authors.lastname: Ha
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Jeon
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Ryoo
authors.forename: Jang-Soo
authors.initials: JS
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D011087:Polycythemia Vera / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: JAK2 V617F; TET2; myeloproliferative neoplasm