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

Omar Abdel‐Wahab(Memorial Sloan Kettering Cancer Center), Ann Mullally(Brigham and Women's Hospital), Cyrus V. Hedvat(Memorial Sloan Kettering Cancer Center), Guillermo Garcia‐Manero(The University of Texas MD Anderson Cancer Center), Jay Patel, Martha Wadleigh(Dana-Farber Cancer Institute), Sébastien Malinge(Northwestern University), JinJuan Yao(Memorial Sloan Kettering Cancer Center), Outi Kilpivaara, Rukhmi Bhat(Northwestern University), Kety Huberman, Sabrena Thomas, Igor Dolgalev, Adriana Heguy, Elisabeth Paietta(Montefiore Medical Center), Michelle M. Le Beau(University of Chicago), Miloslav Beran(The University of Texas MD Anderson Cancer Center), Martin S. Tallman(Northwestern University), Benjamin L. Ebert(Broad Institute), Hagop M. Kantarjian(The University of Texas MD Anderson Cancer Center), Richard M. Stone(Dana-Farber Cancer Institute), D. Gary Gilliland(Broad Institute), John D. Crispino(Northwestern University), Ross L. Levine(Memorial Sloan Kettering Cancer Center)
Blood
May 7, 2009
10.1182/blood-2009-03-210039
Cited by 717Open Access
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Abstract

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.

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