Acquired mutations in TET2 are common in myelodysplastic syndromes

• Published in: Nature genetics Vol. 41; no. 7; pp. 838 - 842
• Main Authors: Jansen, Joop H, Langemeijer, Saskia M C, Kuiper, Roland P, Berends, Marieke, Knops, Ruth, Aslanyan, Mariam G, Massop, Marion, Stevens-Linders, Ellen, van Hoogen, Patricia, van Kessel, Ad Geurts, Raymakers, Reinier A P, Kamping, Eveline J, Verhoef, Gregor E, Verburgh, Estelle, Hagemeijer, Anne, Vandenberghe, Peter, de Witte, Theo, van der Reijden, Bert A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Antigens, CD34 - metabolism; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cancer Research; Care and treatment; Cells; Chromosome aberrations; Chromosomes; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Gene Dosage; Gene Function; Gene mutations; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Granulocytes; Health aspects; Hematologic and hematopoietic diseases; Human Genetics; Humans; letter; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mutation; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Risk factors; Stem Cells - metabolism; Netherlands; Malignant hemopathy; Mutation; Myelodysplastic syndrome; Cancer
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.391

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.