Acquired mutations in TET2 are common in myelodysplastic syndromes

Saskia M C Langemeijer, Roland P Kuiper, Marieke Berends, Ruth Knops, Mariam G Aslanyan, Marion Massop, Ellen Stevens-Linders, Patricia van Hoogen, Ad Geurts van Kessel, Reinier A P Raymakers, Eveline J Kamping, Gregor E Verhoef, Estelle Verburgh, Anne Hagemeijer, Peter Vandenberghe, Theo de Witte, Bert A van der Reijden, Joop H Jansen

Research output: Contribution to journalArticlepeer-review

643 Citations (Scopus)


Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders. Several recurrent chromosomal aberrations have been associated with MDS, but the genes affected have remained largely unknown. To identify relevant genetic lesions involved in the pathogenesis of MDS, we conducted SNP array-based genomic profiling and genomic sequencing in 102 individuals with MDS and identified acquired deletions and missense and nonsense mutations in the TET2 gene in 26% of these individuals. Using allele-specific assays, we detected TET2 mutations in most of the bone marrow cells (median 96%). In addition, the mutations were encountered in various lineages of differentiation including CD34(+) progenitor cells, suggesting that TET2 mutations occur early during disease evolution. In healthy tissues, TET2 expression was shown to be elevated in hematopoietic cells with highest expression in granulocytes, in line with a function in myelopoiesis. We conclude that TET2 is the most frequently mutated gene in MDS known so far.

Original languageEnglish
Pages (from-to)838-42
Number of pages5
JournalNature Genetics
Issue number7
Publication statusPublished - Jul 2009
Externally publishedYes


  • Antigens, CD34/metabolism
  • DNA-Binding Proteins/genetics
  • Dioxygenases
  • Gene Dosage
  • Genetic Predisposition to Disease
  • Humans
  • Myelodysplastic Syndromes/genetics
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins/genetics
  • Stem Cells/metabolism


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