Development of CGH array system and its application for personalized medicine in oral oncology and clinics

CGH阵列系统的开发及其在口腔肿瘤和临床中个体化医疗的应用

• 批准号: 12357012
• 负责人: AMAGASA Teruo
• 金额: $ 23.1万
• 依托单位: Tokyo Medical & Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12357012/
• 关键词: oral cancer; gene amplification; CGH array; cancer-related gene; oncogene; personalized medicine; 染色体; ゲノム; 遺伝子; マイクロアレイ; CGH; 口腔癌; DNA; 一次構造; FISH

Accumulated evidence suggests that multiple genetic alterations occurring sequentially in a cell lineage, at the nucleotide levels as well as at the chromosome levels, underlie the carcinogenetic process in gastrointestinal tumors. Gene amplification is one of the mechanisms capable of activating genes that are implicated in developing tumors. Oncogenes are known to be activated by amplification in squamous cell carcinoma (SCC). By using CGH we performed extensive analysis of copy number aberrations in several types of tumors including oral SCCs. A total number of 800 tumors was analyzed and we could identify target genes within novel amplicons. Furthermore, we have constructed high-density CGH array systems as follows ; (1) an array harboring 4500 BACs throughout whole genome for exploring cryptic chromosome aberrations, (2) an array containing 800 cancer-related genes for "personalized medicine for cancer", and (3) an array harboring 212 BACs spanning the 20 Mb contig at chromosome 1p36. Our tools can open the window for exploring cryptic chromosome aberrations associated with pathogenesis in human tumors.

积累的证据表明，在细胞谱系，核苷酸水平以及染色体水平上依次发生多种遗传改变，这是胃肠道肿瘤中的致癌过程。基因扩增是能够激活与发展肿瘤有关的基因的机制之一。已知癌基因通过在鳞状细胞癌（SCC）中扩增而激活。通过使用CGH，我们对包括口服SCC在内的几种类型的肿瘤进行了广泛的分析。总共分析了800个肿瘤，我们可以鉴定出新型扩增子中的靶基因。此外，我们已经构建了高密度的CGH阵列系统。 （1）整个基因组中携带4500个BAC的阵列，用于探索隐秘的染色体畸变，（2）一个阵列，其中包含800个与癌症相关的基因“个性化癌症”，以及（3）一个载有212个BAC的阵列，跨越了212个BAC，横跨染色体1p36的20 MB重叠群。我们的工具可以打开窗口，以探索与人类肿瘤发病机理相关的隐秘染色体畸变。

项目成果

Yang Z-Q, et al.: "A novel amplification harboring NFIB proximal to GASC1 at 9p23-24 In squamous cell carcinoma of the esophagus"J Cancer Res. 92(4). 423-428 (2001)

Yang Z-Q 等人：“食管鳞状细胞癌中 9p23-24 处 GASC1 附近带有 NFIB 的新型扩增”J Cancer Res。

Michi Y, et al.: "Human oral squamous cell carcinoma cell lines promote angiogenesis via expression of vascular endothelial growth factor and upregulation of KDR/flk-J expression in endothelial cells."Oral Oncology. 36・1. 81-88 (2000)

Michi Y 等人：“人类口腔鳞状细胞癌细胞系通过血管内皮生长因子的表达和内皮细胞中 KDR/flk-J 表达的上调促进血管生成。”口腔肿瘤学 36・1（2000 年）。 ）

Saito-Ohara F, Imoto I, Inazawa J, et al.: "PPM1D is a potential Target for 17q Gain in Neuroblastoma"Cancer Research. (印刷中). (2003)

Saito-Ohara F、Imoto I、Inazawa J 等人：“PPM1D 是神经母细胞瘤中 17q 增益的潜在靶点”癌症研究（出版中）。

Nakakuki K, Imoto I, Amagasa T, Inazawa J, et al.: "Novel targets for the l8p 11.3 amplificaflon frequently observed in esophageal squamous cell carcinomas"Carcinogenesis. 23・1. 19-24 (2002)

Nakakuki K、Imoto I、Amagasa T、Inazawa J 等人：“食管鳞状细胞癌中常见的 l8p 11.3 扩增的新靶标”23・1 (2002)。

Okamoto R, Inazawa J, et al.: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract"Nat Med. 8. 1011-1017 (2002)

Okamoto R、Inazawa J 等人：“人胃肠道中骨髓衍生细胞再生的受损上皮细胞”Nat Med。