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

   


Authors: Abdel-Wahab, O.; Mullally, A.; Hedvat, C.; Garcia-Manero, G.; Patel, J.; Wadleigh, M.; Malinge, S.; Yao, J.; Kilpivaara, O.; Bhat, R.; Huberman, K.; Thomas, S.; Dolgalev, I.; Heguy, A.; Paietta, E.; Le Beau, M. M.; Beran, M.; Tallman, M. S.; Ebert, B. L.; Kantarjian, H. M.; Stone, R. M.; Gilliland, D. G.; Crispino, J. D.; Levine, R. L.
Article Title: Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies
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. © 2009 by The American Society of Hematology.
Keywords: cancer survival; myeloproliferative disorders; survival rate; carrier protein; ten eleven translocation 1; ten eleven translocation 2; ten eleven translocation 3; unclassified drug; dna binding protein; oncoprotein; tet1 protein, human; tet2 protein, human; acute granulocytic leukemia; chronic myelomonocytic leukemia; gene cluster; gene mutation; gene sequence; gene translocation; genetic trait; human cell; major clinical study; methylation; overall survival; promoter region; sequence analysis; single nucleotide polymorphism; somatic mutation; case control study; exon; frameshift mutation; gene deletion; genetics; missense mutation; mutation; myeloproliferative disorder; stop codon; case-control studies; codon, nonsense; dna-binding proteins; exons; leukemia, myeloid, acute; leukemia, myelomonocytic, chronic; mutation, missense; polymorphism, single nucleotide; proto-oncogene proteins; sequence deletion
Journal Title: Blood
Volume: 114
Issue: 1
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2009-07-02
Start Page: 144
End Page: 147
Language: English
DOI: 10.1182/blood-2009-03-210039
PUBMED: 19420352
PROVIDER: scopus
PMCID: PMC2710942
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-67651065502&partnerID=40&md5=984463d5240de26620bd5b799f521853
Notes: --- - "Cited By (since 1996): 39" - "Export Date: 30 November 2010" - "CODEN: BLOOA" - "Source: Scopus"
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MSK Authors
  1. Adriana Heguy
    88 Heguy
  2. Cyrus Hedvat
    126 Hedvat
  3. Jinjuan Yao
    59 Yao
  4. Ross Levine
    776 Levine
  5. Outi Kilpivaara
    12 Kilpivaara
  6. Kety H Huberman
    34 Huberman
  7. Igor Dolgalev
    11 Dolgalev
  8. Omar Ibrahim Abdel-Wahab
    573 Abdel-Wahab
  9. Jay Prakash Patel
    54 Patel
  10. Sabrena Antonette Thomas
    3 Thomas
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