Identification of gene targets for molecular diagnosis and therapeutics in hematopoietic malignancies based on advanced genomics

基于先进基因组学的造血系统恶性肿瘤分子诊断和治疗的基因靶点鉴定

• 批准号: 20390266
• 负责人: OGAWA Seishi
• 金额: $ 11.9万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390266/
• 关键词: ゲノミクス; 分子標的; 造血器腫瘍; 遺伝子診断; ゲノム異常; SNPアレイ; リシーケンス; MDS; ゲノム解析; 遺伝子変異; ATL; HTLV-1; CD2; CD28; BCL11B

Hematopoietic neoplasms are caused by genetic alterations and as such, it is essential to identify the spectrum of genetic changes incriminated in the neoplastic processes for the development of novel diagnostics and therapeutics. In this study, we performed comprehensive genetic analyses of more than 2,000 hematopoietic neoplasms using high-density SNP arrays. Though the high-throughput analysis we identified a number of genetic changes that are relevant to the pathogenesis of hematopoietic neoplasms, including mutations of c-CBL and IDH1/2 in myelodysplastic syndromes, and inactivating mutation/deletion of A20 in non-Hodgkin lymphoma. Combined with subsequent functional studies on these mutations, our finding provide an important insight into the molecular pathogenesis of hemaopoietic malignancies.

造血系统肿瘤是由遗传改变引起的，因此，识别肿瘤过程中涉及的遗传变化谱对于开发新的诊断和治疗方法至关重要。在这项研究中，我们使用高密度SNP阵列对2,000多例造血肿瘤进行了全面的遗传分析。通过高通量分析，我们发现了许多与造血系统肿瘤发病相关的基因改变，包括骨髓增生异常综合征中的c-CBL和IDH 1/2突变，以及非霍奇金淋巴瘤中的A20失活突变/缺失。结合随后对这些突变的功能研究，我们的发现为造血系统恶性肿瘤的分子发病机制提供了重要的见解。

项目成果

Gain-of-function mutations of c-Cb1 tumor suppressor in MDS and MDS/MPD associated with 11q UPD

与 11q UPD 相关的 MDS 和 MDS/MPD 中 c-Cb1 肿瘤抑制因子的功能获得突变

• 发表时间: 2009
• 作者: 真田昌;ら
• 通讯作者: ら

Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array

• DOI: 10.1159/000155813
• 发表时间: 2008-01-01
• 期刊: ONCOLOGY
• 影响因子: 3.5
• 作者: Lin, Lian-Jie;Asaoka, Yoshinari;Omata, Masao
• 通讯作者: Omata, Masao

Hepatoblastoma in a Patient with Sotos Syndrome

• DOI: 10.1016/j.jpeds.2009.06.039
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: Kato, Motohiro;Takita, Junko;Igarashi, Takashi
• 通讯作者: Igarashi, Takashi

Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens

• DOI: 10.1182/blood-2009-10-248997
• 发表时间: 2010-05-13
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Warren, Edus H.;Fujii, Nobuharu;Riddell, Stanley R.
• 通讯作者: Riddell, Stanley R.

Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion

• DOI: 10.1016/j.bbrc.2010.03.120
• 发表时间: 2010-04-16
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Asaoka, Yoshinari;Tada, Motohisa;Koike, Kazuhiko
• 通讯作者: Koike, Kazuhiko