Sallinen S L, Sallinen P K, Haapasalo H K, Helin H J, Helén P T, Schraml P, Kallioniemi O P, Kononen J
Department of Pathology, Tampere University Hospital, Finland.
Cancer Res. 2000 Dec 1;60(23):6617-22.
New genomic large-scale screening techniques have made the task of establishing an accurate molecular fingerprint of cancer cells feasible. Here, we have used a two-phase strategy for identification of molecular alterations in gliomas. First, cDNA microarrays (Clontech Laboratories, Inc., Research Genetics) were used to pinpoint differentially expressed genes between normal brain and diffuse astrocytomas (grades II-IV), and between a primary tumor and a later tumor reoccurrence in the same patient. More than 200 gene expression alterations were detected from glioblastomas, whereas relatively few changes were seen in grade II and grade III tumors. The most distinct progression-related expression change was the up-regulation of the insulin-like growth factor binding protein 2 (IGFBP2) gene. Second, a high-density tissue microarray of 418 brain tumors was constructed and used for clinical validation of gene expression changes. Strong expression of IGFBP2 was associated with progression and poor patient survival in diffuse astrocytomas (P < 0.0001). Third, comparisons of the data between (a) multiple spots retrieved from one predefined tumor region (IGFBP2 and vimentin immunohistochemistry, 20 tumors) or between (b) standard slides and arrayed tissues (p53 immunohistochemistry, 42 tumors) revealed very little variation. In conclusion, the combined use of DNA microarrays and tissue microarrays offers a powerful strategy for rapid identification and thorough characterization of differentially expressed genes in gliomas.
新的基因组大规模筛选技术使建立癌细胞精确分子指纹的任务变得可行。在此，我们采用了两阶段策略来鉴定神经胶质瘤中的分子改变。首先，使用cDNA微阵列（Clontech Laboratories公司，Research Genetics）来确定正常脑与弥漫性星形细胞瘤（II-IV级）之间以及同一患者的原发性肿瘤与后期肿瘤复发之间差异表达的基因。从胶质母细胞瘤中检测到200多个基因表达改变，而在II级和III级肿瘤中观察到的变化相对较少。最明显的与进展相关的表达变化是胰岛素样生长因子结合蛋白2（IGFBP2）基因的上调。其次，构建了一个包含418个脑肿瘤的高密度组织微阵列，并用于基因表达变化的临床验证。在弥漫性星形细胞瘤中，IGFBP2的强表达与进展和患者预后不良相关（P < 0.0001）。第三，对（a）从一个预定义肿瘤区域获取的多个样本点（IGFBP2和波形蛋白免疫组织化学，20个肿瘤）或（b）标准玻片与阵列组织（p53免疫组织化学，42个肿瘤）之间的数据进行比较，发现差异很小。总之，DNA微阵列和组织微阵列的联合使用为快速鉴定和全面表征神经胶质瘤中差异表达的基因提供了一个强大的策略。
