High-resolution profiling of copy-number aberrations in osteosarcoma

Osteosarcoma is a rare, highly malignant tumor of the bone that presents with a highly complex and abnormal karyotype. Only a few of the genes, which are targets of genetic alteration are known. An integrated genome-wide genomic and gene expression profiling analysis was performed on human osteosarcoma tissues and osteosarcoma cell lines in order to identify and map, in a high-resolution fashion, the most drastic chromosomal changes and point out genes which could contribute to tumorigenesis by having altered expression levels of critical oncogenes and tumor suppressors. Combined gene expression and aCGH analysis on the same samples enables direct comparison between DNA and mRNA level and offers a general strategy to identify and prioritize potential targets while the parallel analysis on cell lines offers a reliable models for further functional studies. An integrated genomewide DNA and RNA level data was performed to achieve more accurate information about the target genes involved in the region of gain and loss that present with a consistent expression pattern of variation. 40 osteosarcoma tumor specimens, 12 osteosarcoma cell lines, 1 osteoblast cell line

骨肉瘤（Osteosarcoma）是一种罕见的高度恶性骨肿瘤，其核型呈现高度复杂且异常的特征。目前仅明确少数作为遗传改变靶点的基因。本研究针对人类骨肉瘤组织与骨肉瘤细胞系，开展整合全基因组分析与基因表达谱分析，以期以高分辨率方式精准识别并定位最显著的染色体变异，并阐明可通过改变关键致癌基因与抑癌基因的表达水平参与肿瘤发生的相关基因。对同一样本联合进行基因表达与阵列比较基因组杂交（array Comparative Genomic Hybridization, aCGH）分析，可实现DNA与mRNA水平的直接比对，为识别并优先筛选潜在靶点提供通用研究策略；而对细胞系的平行分析则可为后续功能研究提供可靠的实验模型。本研究通过整合全基因组DNA与RNA水平数据，以期更精准地获取染色体拷贝数增减区域中存在一致性表达变异模式的靶点基因相关信息。本数据集包含40份骨肉瘤肿瘤标本、12株骨肉瘤细胞系及1株成骨细胞系。