British Columbia Cancer Research Center, Vancouver, British Columbia, Canada.
J Mol Diagn. 2011 May;13(3):289-96. doi: 10.1016/j.jmoldx.2010.11.020. Epub 2011 Mar 31.
Osteosarcoma is a genetically complex malignancy, predominantly afflicting the adolescent population and associated still with relatively poor long-term outcomes. Although there has been some improvement in the understanding of osteosarcoma biology, this has not yet translated particularly well into therapeutic advances. By using a whole-genome tiling path array for comparative genomic hybridization analysis, we sought to evaluate DNA copy number changes in 22 osteosarcoma tumor samples. Regions of most frequent gains or losses generated by Genomic Identification of Significant Targets in Cancer analysis were evaluated for genes of interest. Correlation of the copy number data with preexisting expression data for these genes yielded not only targets known to be important in osteosarcoma but also novel targets, notably cyclin E1. Fluorescence in situ hybridization and immunohistochemical analysis confirmed the findings. Overexpression of cyclin E1 has potential prognostic and therapeutic implications that are discussed herein.
骨肉瘤是一种遗传复杂的恶性肿瘤，主要影响青少年人群，其长期预后仍相对较差。尽管人们对骨肉瘤的生物学特性有了一定的了解，但这尚未特别好地转化为治疗进展。通过使用全基因组平铺路径阵列进行比较基因组杂交分析，我们试图评估 22 个骨肉瘤肿瘤样本中的 DNA 拷贝数变化。通过癌症基因鉴定的基因组识别分析生成的最常见增益或丢失区域，评估了感兴趣的基因。将这些基因的拷贝数数据与预先存在的表达数据进行相关性分析，不仅得到了已知在骨肉瘤中重要的靶标，还得到了一些新的靶标，特别是细胞周期蛋白 E1。荧光原位杂交和免疫组织化学分析证实了这些发现。细胞周期蛋白 E1 的过表达具有潜在的预后和治疗意义，本文对此进行了讨论。
