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，多种基因突变的累积可能导致耐药表型。在我们目前的研究中，寻找耐药肿瘤特有的基因变化。我们用比较基因组杂交的方法研究了口腔鳞状细胞癌全基因组的基因异常。这些肿瘤包括25例来自顺铂化疗无效患者的肿瘤和25例来自化疗完全有效患者的肿瘤。我们发现染色体1q25-26、8q24、7q22-31、13q12-14、13q31-34、20q13区域的增加与鳞癌的耐药表型有关，6p12-13、17q13.1、18q21-33的缺失与鳞癌的耐药表型有关。几个编码转录因子、癌基因、细胞周期调节因子和细胞周期调节因子的基因位于染色体的这些区域，根据比较遗传杂交分析，这些基因是口腔癌患者某些基因组异常与临床对顺铂化疗耐药之间的潜在毒性调节因子。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