MOLECULAR ANALYSIS OF CANCER FAMILY SYNDROME

癌症家族综合症的分子分析

• 批准号: 10670719
• 负责人: KANEKO Hideo
• 金额: $ 2.05万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670719/
• 关键词: BLOOM SYNDROME; BLM; ATAXIA-TELANGIECTASIA; ATM; FAMILIAL TUMOR; IMMUNODEFICIENCY; 相合作用; イムノブロット; ヘリカーゼ活性; 核移行シグナル

(1) We showed that BLM protein was expressed strongly in thymus and testis and that BLM protein was not directly involved in Ig VDJ recombination.(2) We showed that the ArgィイD11344ィエD1-SerィイD11345ィエD1-LysィイD11346ィエD1-ArgィイD11347ィエD1 sequence at the C-terminus of the human BLM protein was essential for nuclear localization of this protein.(3) We demonstrated that immunoblot analysis using EBV-transformed or PHA-stimulated lymphoblastas represented a useful approach for laboratory diagnosis for A-T.(4) We demonstrated that ATM is upregulated during the mitogenic response in peripheral blood mononuclear cells.(5) We showed that IVS33 + 2T -> A and 7883del5 were identified in four and five alleles, respectively, in a total of 18 mutant alleles of Japanese A-T patients. These results suggested that these two mutations were relatively common mutations in the Japanese population.

(1)我们发现BLM蛋白在胸腺和睾丸中强烈表达，并且BLM蛋白不直接参与IG VDJ重组。(2)我们发现，在人BLM蛋白C-末端的Arg精氨酸D11344精氨酸D11345丝氨酸D11345赖氨酸D11346赖氨酸D11347精氨酸D11347精氨酸D1序列是该蛋白的核定位所必需的。(3)我们证明了使用EBV转化或PHA刺激的淋巴母细胞进行免疫印迹分析是一种有用的实验室诊断A-T的方法。(4)我们证明ATM在外周血单个核细胞的促有丝分裂反应过程中上调。(5)我们发现，在日本A-T患者的总共18个突变等位基因中，分别在4个和5个等位基因中鉴定出IVS 33 + 2 T-> A和7883 del 5。这些结果表明，这两种突变是日本人群中相对常见的突变。

项目成果

Matsui E, Kaneko H, et al: "Reduced IFN-gammma production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients"Clin. Exp. Allergy. (in press).

Matsui E、Kaneko H 等人：“响应 IL-12 刺激而减少 IFN-γ 产生和/或特应性患者中 IL-12 产生减少”Clin。

Fukao, T., Kaneko, H., Birrell, G., Gatei, M., Tashita, H., Kasahara K., Cross, S., Kedar, P., Watters, D., Khanna, K.K., Misko, I., Kondo, N. and Lavin, M.F.: "ATM is upregulated during the mitogenic response in peripheral blood mononuclear cells."Blood.

Fukao, T.、Kaneko, H.、Birrell, G.、Gatei, M.、Tashita, H.、笠原 K.、Cross, S.、Kedar, P.、Watters, D.、Khanna, K.K.、Misko,

Hayakawa S., Kaneko H., Fukao T., Kasahara K., Matsumoto T., Furuichi Y. and Kondo N.: "Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome."Int. J. Mol. Med.. (in press).

Hayakawa S.、Kaneko H.、Fukao T.、Kasahara K.、Matsumoto T.、Furuichi Y. 和 Kondo N.：“负责布卢姆综合征的 DNA 解旋酶中核定位信号的表征。”Int。

Fukao T, Kaneko H, et al: "A novel exonic mutation (5319* G to A) resulting in two aberrantly spliced transcripts of the ATM gene in a Japanese patient with ataxia-telangiectasia"Human mutation. 5223-5225 (1998)

Fukao T、Kaneko H 等人：“一种新的外显子突变（5319* G 到 A）导致日本共济失调毛细血管扩张症患者的 ATM 基因的两个异常剪接转录本”人类突变。

Yamada Y, Kaneko H, et al: "Ataxia telangiectasia associated with B-cell lymphoma"Pediatr. Hematol. Oncol.. 15. 425-429 (1998)

Yamada Y、Kaneko H 等人：“与 B 细胞淋巴瘤相关的共济失调性毛细血管扩张”Pediatr。