Presneau Nadège, Mes-Masson Anne-Marie, Ge Bing, Provencher Diane, Hudson Thomas J, Tonin Patricia N
Research Institute of the McGill University Helath Centre, Montréal, Quebéc, Canada.
Oncogene. 2003 Mar 13;22(10):1568-79. doi: 10.1038/sj.onc.1206219.
Oligonucleotide microarray analysis was applied to assess the expression profile of 332 probe sets representing 308 genes or expressed sequence tags (ESTs) that map to chromosome 17 in order to address epigenetic events that result in alterations in gene expression in epithelial ovarian cancer (EOC). Expression profiles were generated from 12 primary cultures derived from normal ovarian surface epithelium (NOSE) and four long-term cultures (TOV-81D, TOV-112D, TOV-21G and OV-90) derived from EOCs that have been previously characterized and shown to mimic features of the tumoral cells from which they were derived. The expression values of all 332 probe sets is highly correlated across the 12 NOSEs (89% correlation coefficients >0.90). In two-way comparisons, differential patterns of gene expression were observed for 157 probe sets for which the expression value of at least one EOC cell line fell outside the limits of the range of expression of the 12 NOSEs. When compared to NOSEs, four genes displayed similar differential patterns of gene expression across all four EOC cell lines, and 26 genes displayed similar differential patterns of gene expression across the three EOC cell lines (TOV-112D, TOV-21G and OV-90) representing tumoral cells derived from the most aggressive disease. A total of 17 genes displayed differential patterns of gene expression greater than threefold in at least one EOC cell line in comparison to NOSE, and three genes were differentially expressed greater than threefold across all aggressive cell lines. The analysis of a selected number of genes by RT-PCR revealed patterns of gene expression comparable to those observed by microarray analysis in the majority of samples tested. Comparison of expression profiles of differentially expressed genes identified by microarray analysis in two-way comparisons of the EOC cell lines and the NOSEs with published reports revealed 10 genes previously implicated in ovarian tumorigenesis and 18 in tumorigenesis of other types of cancer. The differential pattern of gene expression of genes that map to both the p and q arm of chromosome 17 is consistent with the hypothesis that a number of genes that map to this chromosome are implicated in the etiology of ovarian cancer.
应用寡核苷酸微阵列分析来评估代表308个基因或表达序列标签（EST）的332个探针集的表达谱，这些基因或EST定位于17号染色体，以研究导致上皮性卵巢癌（EOC）基因表达改变的表观遗传事件。表达谱来自12个源自正常卵巢表面上皮（NOSE）的原代培养物和4个源自EOC的长期培养物（TOV-81D、TOV-112D、TOV-21G和OV-90），这些EOC先前已被表征，并显示出与其来源的肿瘤细胞特征相似。在12个NOSE样本中，所有332个探针集的表达值高度相关（89%的相关系数>0.90）。在双向比较中，观察到157个探针集的基因表达差异模式，其中至少一个EOC细胞系的表达值超出了12个NOSE样本的表达范围。与NOSE相比，4个基因在所有4个EOC细胞系中表现出相似的基因表达差异模式，26个基因在代表源自侵袭性最强疾病的肿瘤细胞的3个EOC细胞系（TOV-112D、TOV-21G和OV-90）中表现出相似的基因表达差异模式。与NOSE相比，共有17个基因在至少一个EOC细胞系中的基因表达差异模式大于三倍，3个基因在所有侵袭性细胞系中的差异表达大于三倍。通过RT-PCR对选定数量的基因进行分析，结果显示在大多数测试样本中，基因表达模式与微阵列分析观察到的模式相当。将微阵列分析在EOC细胞系和NOSE的双向比较中鉴定出的差异表达基因的表达谱与已发表的报告进行比较，发现10个基因先前与卵巢肿瘤发生有关，18个基因与其他类型癌症的肿瘤发生有关。定位于17号染色体p臂和q臂的基因的基因表达差异模式与以下假设一致，即许多定位于该染色体的基因与卵巢癌的病因有关。
