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

口腔鳞状细胞癌耐药机制是多因素的，多种基因变异的累积可能导致耐药表型的产生。在我们目前的研究中，寻找耐药肿瘤的特征性遗传变化。我们采用比较基因组杂交方法研究了原发性口腔鳞状细胞癌全基因组的基因畸变。这些癌症包括来自对顺铂化疗无反应的患者的25个肿瘤和来自对化疗有完全反应的患者的25个肿瘤。结果发现1 q25 -26、8 q24、7 q22 -31、13 q12 -14、13 q31 -34、20 q13区域的增加与鳞状细胞癌的耐药表型有关，6p 12 - 13、17q13.1、18 q21 -33区域的丢失与鳞状细胞癌的耐药表型有关。几个基因编码的转录因子，癌基因，细胞周期调控因子，和调节器的凋亡途径位于这些区域的染色体，这些基因是潜在的调制器之间的某些基因组畸变的毒性损伤和临床耐药的口腔癌患者顺铂化疗的基础上比较遗传杂交分析。这些发现表明，这些染色体的获得和丢失可能是预测抗性的潜在指标。

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.