Genome research on interindividual variations on drug response and application of genetic diagnosis to personalized medicine

药物反应个体差异的基因组研究及基因诊断在个体化医疗中的应用

• 批准号: 15390619
• 负责人: SHINOHARA Masanori
• 金额: $ 9.09万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390619/
• 关键词: drug response; antitumor agent; drug delivery; genetic diagnosis; drug resistance; personalized medicine; CGH; ゲノム遺伝子解析; 薬剤感受性; 個別化治療; CGH法

The mechanism of drug resistance in oral squamous cell carcinoma is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our present study to find characteristic genetic changes in drug-resistant tumors. We investigated the whole genome for gene aberrations in primary oral squamous cell carcinomas using the comparative genomic hybridization method. These cancers included 25 tumors from patient who did not respond to cisplatin chemotherapy and 25 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q25-26,8q24,7q22-31,13q12-14,13q31-34,20q13 to be related to the drug-resistant phenotype in squamous cell carcinoma and loss in6p12-13,17q13.1,18q21-33 to be related to the drug-resistant phenotype in squamous cell carcinoma. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in ship between certain genomic aberrations for and clinical resistance to cisplatin chemotherapy in oral cancer patients based on the comparative genetic hybridization analysis. These finding suggest that these chromosomal gains and loss may be potential indicators for prediction of resistance.

口腔鳞状细胞癌的耐药机制是多因素的，多种基因改变的积累可能导致耐药表型。在我们目前的研究中，寻找耐药肿瘤的特征性遗传变化。我们使用比较基因组杂交方法研究了原发性口腔鳞状细胞癌的全基因组基因畸变。这些癌症包括 25 个来自对顺铂化疗无反应的患者的肿瘤和 25 个来自对化疗有完全反应的患者的肿瘤。我们发现染色体区域1q25-26,8q24,7q22-31,13q12-14,13q31-34,20q13的增加与鳞状细胞癌的耐药表型相关，而6p12-13,17q13.1,18q21-的缺失与耐药表型相关。 33与鳞状细胞耐药表型有关癌。编码转录因子、癌基因、细胞周期调节因子和细胞凋亡途径调节因子的几个基因位于染色体的这些区域，这些基因是某些基因组畸变和顺铂化疗临床耐药之间的毒性损伤的潜在调节剂。基于比较遗传杂交分析的口腔癌患者。这些发现表明，这些染色体的获得和丢失可能是预测耐药性的潜在指标。

项目成果

NF-kB involvement in tumor-stroma interaction of squamous cell carcinoma.

NF-kB 参与鳞状细胞癌的肿瘤-基质相互作用。

• 发表时间: 2004
• 期刊: Oral Omcology 40
• 作者: Ikebe;T
• 通讯作者: T