Exploring new gene target of 4q-UPD in Myelodysplastic syndromes

应用高分辨率单核苷酸多态性（SNP）基因芯片检测MDS患者DNA拷贝数改变和杂合性丢失（洛），发现约30%的MDS患者存在拷贝数中性洛（aUPD）。我们鉴定了涉及4 q24的复发性aUPD，并通过靶测序鉴定了TET 2突变。我们还对20例MDS样本进行了全外显子组分析，其中使用SureSelect Human All Exon试剂盒富集了整个外显子序列，并使用Genome Analizer IIx进行了重测序分析。通过比较肿瘤和配对T细胞中的序列，总共检测到近200个体细胞突变和10个插入-缺失。我们的研究结果表明，靶捕获重测序技术是一种强有力的方法，以确定新的基因突变，参与MDS的发病机制。

Using high resolution single nucleotide polymorphism (SNP) microarrays to examine DNA copy number alterations and loss of heterozygosity (LOH), copy-number neutral LOH (aUPD) were seen in about 30% cases of MDS. We identified recurring aUPD involving 4q24 and led to the identification of TET2 mutations by target sequencing. We also conducted whole exome analysis of 20 MDS samples, where entire exon sequences were enriched by using SureSelect Human All Exon kit and were subjected to resequencing analysis using Genome Analizer IIx. By comparing sequences in tumors and paired T cells, nearly 200 somatic mutations and 10 insertions-deletions were detected in total. Our results suggested that target-capture resequencing technology is a powerful method to identify new gene mutations that are implicated in the pathogenesis of MDS.