Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Leukemia, Myeloid, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Mutation
  • Proto-Oncogene Proteins

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.

publication date

  • November 18, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2710942

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-03-210039

PubMed ID

  • 19420352

Additional Document Info

start page

  • 144

end page

  • 7

volume

  • 114

number

  • 1