Acquired mutations in TET2 are common in myelodysplastic syndromes
Acquired mutations in TET2 are common in myelodysplastic syndromes
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DOI：
10.1038/ng.391
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发表时间：
2009-07-01
期刊：
影响因子：
30.8
通讯作者：
Jansen, Joop H.
中科院分区：
文献类型：
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作者：
Langemeijer, Saskia M. C.;Kuiper, Roland P.;Jansen, Joop H.
骨髓增生异常综合征（MDS）是一组异质性肿瘤性造血系统疾病（1）。几种复发性染色体畸变与MDS相关，但受影响的基因在很大程度上仍然未知。为了确定MDS发病机制中涉及的相关遗传病变，我们对102名MDS患者进行了基于SNP阵列的基因组分析和基因组测序，并在这些患者中的26%中确定了TET2基因的获得性缺失、错义和无义突变。使用等位基因特异性分析，我们在大多数骨髓细胞中检测到TET2突变（中位数96%）。此外，在包括CD34（+）祖细胞在内的各种分化谱系中都会遇到突变，这表明TET2突变发生在疾病演变的早期。在健康组织中，TET2表达在造血细胞中升高，在粒细胞中表达最高，与骨髓生成中的功能一致。我们的结论是，TET2是迄今为止已知的MDS中最常见的突变基因。
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.