Deletion mapping of chromosome band 14q32 for isolation and characterization of the putative tumor related gene in human neuroblastoma

染色体带 14q32 的缺失图谱，用于分离和表征人神经母细胞瘤中假定的肿瘤相关基因

• 批准号: 09470386
• 负责人: HAYASHI Yutaka
• 金额: $ 8.38万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470386/
• 关键词: neuroblastoma; chromosome arm 14q; Positional cloning; LOH; 染色体第14番; 染色体欠失; マイクロサテライトマーカー; FISH; BAC

We are investigating a tumor suppressor gene(s) responsible for neuroblastoma(NB) and we are focusing especially on chromosome arm 14q.As the first step in isolation and characterization of the putative tumor suppressor gene, we constructed a deletion map on chromosome band 14q32 by LOH study using 12 microsatellite markers.In this study, we analyzed 54 tumors and corresponding constitutional tissues of patients with NB.We performed PCR-LOH study using microsatellite markers on 14q32. Seventeen (3 1%) of 54 cases showed loss of heterozygosity on chromosome band 14q32, and an approximately 1-cM region of common deletion was found that was flanked by D14S62 and D14S987. These results were confirmed by FISH analyses using bacterial artificial chromosome (BAG) purchased by this grant and/or cosmid clones isolated from human genomic cosmid library we constructed.Now, we have constructed an approximately 8-cM sequence-ready contig consisting of BAG and cosmid clones that was flanked by D14S62 and D14S267 to isolate and analyze the putative tumor suppressor gene. Our findings support the *istence of putative tumor suppressor gene on 14q32 for the tumorigenesis of NB.Further investigations are required to elucidate the tumorigenesis of NB.

我们正在研究一种与神经母细胞瘤（NB）有关的肿瘤抑制基因，我们特别关注染色体臂14q。作为推定肿瘤抑制基因分离和鉴定的第一步，我们利用12个微卫星标记通过LOH研究构建了染色体带14q32缺失图谱。在本研究中，我们分析了54例NB患者的肿瘤及相应的体质组织。我们利用微卫星标记对14q32进行PCR-LOH研究。54例患者中有17例（31.1%）染色体14q32带杂合性缺失，在D14S62和D14S987的两侧发现约1 cm的共同缺失区。使用本基金购买的细菌人工染色体（BAG）和/或从我们构建的人类基因组cosmid文库中分离的cosmid克隆进行FISH分析证实了这些结果。现在，我们已经构建了一个由BAG和cosmid克隆组成的约8 cm的序列准备序列，其两侧分别是D14S62和D14S267，用于分离和分析推定的肿瘤抑制基因。我们的研究结果支持了14q32上可能存在的肿瘤抑制基因在NB肿瘤发生中的作用。需要进一步的研究来阐明NB的肿瘤发生机制。

项目成果

阿部忠義他: "Identification of three commonly deleted regions on chromosome arm 6g in human pancreatic cancer" Genes Chromosomes Cancer in press. (未定).

Tadayoshi Abe 等人：“人类胰腺癌染色体臂 6g 上三个常见缺失区域的识别”，《基因染色体癌症》待出版。

古川徹他: "Genomic analysis of DUSP6.a dual specificity MAP kinase phosphatase, in pancreatic cancer" Cytogenet. Cell Genet. 82. 156-159 (1998)

Toru Furukawa 等人：“胰腺癌中 DUSP6.a 双重特异性 MAP 激酶磷酸酶的基因组分析”Cytogenet。82. 156-159 (1998)

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