デジタルゲノムスキャニング法の開発と消化器癌関連遺伝子探索への応用

数字基因组扫描方法开发及应用寻找胃肠癌相关基因

• 批准号: 17659415
• 负责人: 時野 隆至
• 金额: $ 2.11万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17659415/
• 关键词: 癌; ゲノム; 遺伝子増幅; 遺伝子欠失

癌遺伝子の増幅や癌抑制遺伝子の欠失を伴う染色体変化はがん細胞の特徴である.本研究では短いゲノム断片を解析しゲノム上のDNAコピー数以上を示す領域を検出する方法としてデジタルゲノムスキャニング(DGS: Digital Genome Scanning)法を開発し,胃癌細胞株におけるゲノムコピー数異常の検出を試みた.胃癌細胞株ゲノムDNAを制限酵素処理した断片を回収し,連結したクローニングしたDNA断片の塩基配列を決定した.取得した塩基配列をヒトゲノム上にマップし,ゲノム上での断片の分布密度をもとにコピー数異常を示す領域を推定した.DGSで予測されたゲノム増幅領域に存在する癌遺伝子の候補については,次に,Southern blot, FISH, real-time RT-PCR, Western blot法などの分子生物学的手法で検証を行った.このDGS解析により,胃癌細胞株の第12番染色体短腕約0.5Mbのゲノム増幅が同定され,同領域に存在する癌遺伝子K-rasのゲノム増幅を確認した.K-ras領域のゲノム増幅は胃癌細胞株18種中4種で,また臨床胃悪性腫瘍50例中4例で検出された.また,K-rasの遺伝子増幅を示した胃癌細胞株ではMAP kinase(ERK1/2)の恒常的活性化が観察された.以上より,DGS法はがんを代表とするゲノムコピー数異常を呈する疾患の原因遺伝子探索において有効な手法となりうることを実証した.

The amplitude of cancer suppressors is deficient with chromosomal metaplasia, and the cells are specially abnormal. In this study, we analyzed the number of DNA fragments in this study, which indicated that the number of samples in the field was higher than that in the field. The method of DGS: Digital Genome Scanning was used to open the test, and the number of cell lines of gastric cancer was tested. Gastric cancer cell line DNA was used to make restriction enzymes, fragments, fragments, DNA fragments, DNA fragments, restriction enzyme, enzyme restriction, enzyme restriction, enzyme In this paper, the distribution density of fragments, the number of fragments, the density of fragments, the number of fragments, the number of fragments, the density of fragments, the number of fragments, the density of fragments, the number of fragments, the density of fragments, the number of fragments, the number The results of DGS analysis showed that the amplitude of chromosome 12 short wrist of gastric cancer cell line was the same as that of 0.5Mb, and the amplitude of K-ras was confirmed in the same field. 4 of 18 kinds of gastric cancer cell lines were found in K-ras field, and 4 of 50 cases of gastric cancer were found in the same field. The constant activation of gastric cancer cell line MAP kinase (ERK1/2) was observed in K-ras cells. In the DGS method, the number of patients often shows the cause of the disease, the cause of the disease and the cause of the disease.

项目成果

Id2 protein is selectively upregulated by UVB in primary, but not in immortalized human keratinocytes and inhibits differentiation

• DOI: 10.1038/sj.onc.1208709
• 发表时间: 2005-08-18
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Simbulan-Rosenthal, CM;Trabosh, V;Rosenthal, DS
• 通讯作者: Rosenthal, DS

Ku70 and poly (ADP-ribose) polymerase-1 competitively regulate beta-catenine and T-cell factor-4-mediated gene transactivation: possible linkage of DNA damage recognition and Wnt signaling.

Ku70 和聚 (ADP-核糖) 聚合酶-1 竞争性调节 β-连环蛋白和 T 细胞因子 4 介导的基因反式激活：DNA 损伤识别和 Wnt 信号传导之间可能存在联系。

• 发表时间: 2007
• 期刊: Cancer Research 67
• 作者: Mita H;et al;Sasaki Y;Kawamura YI;Sasaki Y;Suzuki H;Maruyama R;Imai T;Sogabe Y;Idogawa M
• 通讯作者: Idogawa M

Activation of the ribosomal protein L13 gene in human gastrointestinal cancer.

• DOI: 10.3892/ijmm.18.1.161
• 发表时间: 2006-07
• 期刊: International journal of molecular medicine
• 影响因子: 5.4
• 作者: Toshihisa Kobayashi;Y. Sasaki;Yuichiro Oshima;Hiroyuki Yamamoto;H. Mita;Hiromu Suzuki;M. Toyota

Genetic, epigenetic and clinicopathological features of gastric cancers with CpG island methylator phenotype and association to Epstein-Barr virus.

具有 CpG 岛甲基化表型以及与 Epstein-Barr 病毒相关的胃癌的遗传、表观遗传和临床病理学特征。

• 发表时间: 2006
• 期刊: C a n c e r 106(7)
• 作者: Kusano M;Toyota M;Suzuki H;Akino K;Aoki F;Fujita M;Hosokawa M;Shinomura Y;Imai K;Tokino T
• 通讯作者: Tokino T

Aberrant laminin beta3 isoforms downstream of EWS-ETS fusion genes in Ewing family tumors

尤文家族肿瘤中 EWS-ETS 融合基因下游的异常层粘连蛋白 beta3 亚型

• 发表时间: 2005
• 期刊: Cancer Cell Ther 4
• 作者: Irifune H;Nishimori H;Watanabe G;Yoshida K;Ikeda T;Matsui C;Morohashi M;Kawaguchi S;et al.
• 通讯作者: et al.