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 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.
Langemeijer
Saskia M C
SM
Department of Hematology and Central Hematology Laboratory, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Kuiper
Roland P
RP
Berends
Marieke
M
Knops
Ruth
R
Aslanyan
Mariam G
MG
Massop
Marion
M
Stevens-Linders
Ellen
E
van Hoogen
Patricia
P
van Kessel
Ad Geurts
AG
Raymakers
Reinier A P
RA
Kamping
Eveline J
EJ
Verhoef
Gregor E
GE
Verburgh
Estelle
E
Hagemeijer
Anne
A
Vandenberghe
Peter
P
de Witte
Theo
T
van der Reijden
Bert A
BA
Jansen
Joop H
JH
D018952:Antigens, CD34 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human