Imoto Issei, Inazawa Johji
Dept. of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University.
Gan To Kagaku Ryoho. 2005 Nov;32(12):1891-4.
Tumors develop through the combined processes of genetic instability and selection, resulting in clonal expansion of cells that have accumulated the most advantageous set of genetic aberrations. Many types of instability may occur, resulting in point mutations, chromosomal rearrangements, DNA dosage abnormalities, and epigenetic changes such as methylation. In order to identify novel molecular targets for cancer therapy, we have focused on genomic copy-number aberrations as landmarks. Recent advances in array-based CGH technology (CGH-array) have enabled examination of chromosomal regions in unprecedented detail, prompting us to screen cancer-related genes including candidates of molecular targets. Indeed, applying our in-house CGH-array, we have identified several amplification target oncogenes as well as tumor suppressor genes. Useful molecular targets for cancer therapy will be identified more rapidly through exploring genomic and/or epigenomic abnormalities using genomic arrays including CGH-array system.
肿瘤通过基因不稳定和选择的联合过程发展,导致积累了最有利的一组基因畸变的细胞发生克隆性扩增。可能会出现多种类型的不稳定,导致点突变、染色体重排、DNA剂量异常以及甲基化等表观遗传变化。为了确定癌症治疗的新分子靶点,我们将重点放在基因组拷贝数畸变作为标志物上。基于微阵列的比较基因组杂交技术(CGH微阵列)的最新进展使得能够以前所未有的细节检查染色体区域,促使我们筛选包括分子靶点候选基因在内的癌症相关基因。事实上,应用我们内部的CGH微阵列,我们已经鉴定出了几个扩增靶点癌基因以及肿瘤抑制基因。通过使用包括CGH微阵列系统在内的基因组阵列探索基因组和/或表观基因组异常,将更快地确定癌症治疗的有用分子靶点。