Acquired mutations in TET2 are common in myelodysplastic syndromes
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 M...
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| Published in | Nature genetics Vol. 41; no. 7; pp. 838 - 842 |
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| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.07.2009
Nature Publishing Group |
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| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | 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 super(+) 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. Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders (1). 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.sup.+] 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. 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. Joop Jansen and colleagues show that myelodysplastic syndromes frequently harbor somatic mutations in TET2 . Analysis of lineage markers suggests that TET2 mutations are early events contributing to malignant transformation. Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders 1 . 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. 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^sup +^ 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. [PUBLICATION ABSTRACT] |
| Audience | Academic |
| Author | Jansen, Joop H Raymakers, Reinier A P Verburgh, Estelle van der Reijden, Bert A Stevens-Linders, Ellen Verhoef, Gregor E Aslanyan, Mariam G de Witte, Theo Berends, Marieke Massop, Marion Hagemeijer, Anne Langemeijer, Saskia M C Knops, Ruth van Hoogen, Patricia van Kessel, Ad Geurts Kamping, Eveline J Kuiper, Roland P Vandenberghe, Peter |
| Author_xml | – sequence: 1 givenname: Joop H surname: Jansen fullname: Jansen, Joop H organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 2 givenname: Saskia M C surname: Langemeijer fullname: Langemeijer, Saskia M C organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 3 givenname: Roland P surname: Kuiper fullname: Kuiper, Roland P organization: Department of Human Genetics, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 4 givenname: Marieke surname: Berends fullname: Berends, Marieke organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 5 givenname: Ruth surname: Knops fullname: Knops, Ruth organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 6 givenname: Mariam G surname: Aslanyan fullname: Aslanyan, Mariam G organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 7 givenname: Marion surname: Massop fullname: Massop, Marion organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 8 givenname: Ellen surname: Stevens-Linders fullname: Stevens-Linders, Ellen organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 9 givenname: Patricia surname: van Hoogen fullname: van Hoogen, Patricia organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 10 givenname: Ad Geurts surname: van Kessel fullname: van Kessel, Ad Geurts organization: Department of Human Genetics, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 11 givenname: Reinier A P surname: Raymakers fullname: Raymakers, Reinier A P organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 12 givenname: Eveline J surname: Kamping fullname: Kamping, Eveline J organization: Department of Human Genetics, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 13 givenname: Gregor E surname: Verhoef fullname: Verhoef, Gregor E organization: Hematology, Department of Internal Medicine, University Hospital Leuven – sequence: 14 givenname: Estelle surname: Verburgh fullname: Verburgh, Estelle organization: Hematology, Department of Internal Medicine, University Hospital Leuven – sequence: 15 givenname: Anne surname: Hagemeijer fullname: Hagemeijer, Anne organization: Laboratory for Genetics of Malignant Disorders, Centre for Human Genetics, University Hospital Leuven – sequence: 16 givenname: Peter surname: Vandenberghe fullname: Vandenberghe, Peter organization: Laboratory for Genetics of Malignant Disorders, Centre for Human Genetics, University Hospital Leuven – sequence: 17 givenname: Theo surname: de Witte fullname: de Witte, Theo organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences – sequence: 18 givenname: Bert A surname: van der Reijden fullname: van der Reijden, Bert A organization: Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21684800$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/19483684$$D View this record in MEDLINE/PubMed |
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| CODEN | NGENEC |
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| Snippet | Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders. Several recurrent chromosomal aberrations have been... Joop Jansen and colleagues show that myelodysplastic syndromes frequently harbor somatic mutations in TET2 . Analysis of lineage markers suggests that TET2... Myelodysplastic syndromes (MDS) represent a heterogeneous group of neoplastic hematopoietic disorders (1). Several recurrent chromosomal aberrations have been... |
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| SubjectTerms | 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 |
| Title | Acquired mutations in TET2 are common in myelodysplastic syndromes |
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