TY - JOUR
T1 - Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies
AU - Abdel-Wahab, Omar
AU - Mullally, Ann
AU - Hedvat, Cyrus
AU - Garcia-Manero, Guillermo
AU - Patel, Jay
AU - Wadleigh, Martha
AU - Malinge, Sebastien
AU - Yao, Jin Juan
AU - Kilpivaara, Outi
AU - Bhat, Rukhmi
AU - Huberman, Kety
AU - Thomas, Sabrena
AU - Dolgalev, Igor
AU - Heguy, Adriana
AU - Paietta, Elisabeth
AU - Le Beau, Michelle M.
AU - Beran, Miloslav
AU - Tallman, Martin S.
AU - Ebert, Benjamin L.
AU - Kantarjian, Hagop M.
AU - Stone, Richard M.
AU - Gilliland, D. Gary
AU - Crispino, John D.
AU - Levine, Ross L.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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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U2 - 10.1182/blood-2009-03-210039
DO - 10.1182/blood-2009-03-210039
M3 - Article
C2 - 19420352
AN - SCOPUS:67651065502
SN - 0006-4971
VL - 114
SP - 144
EP - 147
JO - Blood
JF - Blood
IS - 1
ER -