Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies

被引：543

作者：

Abdel-Wahab, Omar ^{[1
,2
]}

Mullally, Ann ^{[3
,4
]}

Hedvat, Cyrus ^{[5
]}

Garcia-Manero, Guillermo ^{[6
]}

Patel, Jay ^{[1
]}

Wadleigh, Martha ^{[3
]}

Malinge, Sebastien ^{[7
]}

Yao, JinJuan ^{[5
]}

Kilpivaara, Outi ^{[1
]}

Bhat, Rukhmi ^{[7
]}

Huberman, Kety ^{[1
]}

Thomas, Sabrena ^{[1
]}

Dolgalev, Igor ^{[1
]}

Heguy, Adriana ^{[1
]}

Paietta, Elisabeth ^{[8
]}

Le Beau, Michelle M. ^{[9
]}

Beran, Miloslav ^{[6
]}

Tallman, Martin S. ^{[7
]}

Ebert, Benjamin L. ^{[4
,10
,11
]}

Kantarjian, Hagop M. ^{[6
]}

Stone, Richard M. ^{[3
]}

Gilliland, D. Gary ^{[4
,10
,12
]}

Crispino, John D. ^{[7
]}

Levine, Ross L. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Dept Med, New York, NY 10065 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[7] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA

[8] New York Med Coll, Montefiore Med Ctr, North Div, New York, NY USA

[9] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA

[10] Harvard Stem Cell Inst, Boston, MA USA

[11] Harvard & Massachusetts Inst Technol, Broad Inst, Boston, MA USA

[12] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

BLOOD | 2009年 / 114卷 / 01期

关键词：

TYROSINE KINASE JAK2; ACTIVATING MUTATION; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE DISORDERS; ESSENTIAL THROMBOCYTHEMIA; HIGH-THROUGHPUT; LEUKEMIA; SEQUENCE; MYELOFIBROSIS; METAPLASIA;

D O I：

10.1182/blood-2009-03-210039

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Disease alleles that activate signal transduction are common in myeloid malignancies; however, there are additional unidentified mutations that contribute to myeloid transformation. Based on the recent identification of TET2 mutations, we evaluated the mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Sequencing of TET2 in 408 paired tumor/normal samples distinguished between 68 somatic mutations and 6 novel single nucleotide polymorphisms and identified TET2 mutations in MPN (27 of 354, 7.6%), CMML (29 of 69, 42%), AML (11 of 91, 12%), and M7 AML (1 of 28, 3.6%) samples. We did not identify somatic TET1 or TET3 mutations or TET2 promoter hypermethylation in MPNs. TET2 mutations did not cluster in genetically defined MPN, CMML, or AML subsets but were associated with decreased overall survival in AML (P = .029). These data indicate that TET2 mutations are observed in different myeloid malignancies and may be important in AML prognosis. (Blood. 2009; 114:144-147)

引用

页码：144 / 147

页数：4

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