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

探索骨髓增生异常综合征中 4q-UPD 的新基因靶标

• 批准号: 21790907
• 负责人: SANADA Masashi
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790907/
• 关键词: 骨髄異形成症候群; ゲノム; 遺伝子変異; LOH

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.

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。

项目成果

Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms

• DOI: 10.1182/blood-2009-07-235119
• 发表时间: 2010-04-08
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Thoennissen, Nils H.;Krug, Utz O.;Koeffler, H. Phillip
• 通讯作者: Koeffler, H. Phillip

骨髄系腫瘍におけるCBL変異の機能解析

髓系肿瘤CBL突变的功能分析

• 发表时间: 2010
• 作者: 真田昌;ら
• 通讯作者: ら

Gain-of-function mutations of c-Cbl tumor suppressor in MDS and MDS/MPD associated with 11qUPD

MDS 和 MDS/MPD 中与 11qUPD 相关的 c-Cbl 肿瘤抑制因子的功能获得突变

• 发表时间: 2009
• 作者: Chiba;T.;et al.;Fumio Nakahara;Masashi Sanada
• 通讯作者: Masashi Sanada

Unique Gain-of-Function of Mutated c-CBL Tumor Suppresor in Myeloid Neoplasms

突变的 c-CBL 肿瘤抑制因子在骨髓肿瘤中获得独特的功能

• 发表时间: 2009
• 作者: 真田昌;ら;真田昌
• 通讯作者: 真田昌

Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.

与骨髓肿瘤中 11q 单亲二体性相关的功能获得性 c-CBL 突变。

• 发表时间: 2010
• 期刊: Cell Cycle. 9
• 作者: Ogawa S;Sanada M;Shih LY;Suzuki T;Otsu M;Nakauchi H;Koeffler HP.
• 通讯作者: Koeffler HP.