Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Neuro Oncol. 2010 Sep;12(9):991-1003. doi: 10.1093/neuonc/noq050. Epub 2010 May 18.
Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.
尽管人们对胶质瘤相关的基因改变和分子途径有了越来越多的了解，但很少有研究调查基因表达谱（GEP）与胶质瘤的细胞遗传学和组织病理学之间的关系。在这里，我们分析了 40 例胶质瘤（35 例星形细胞瘤、3 例少突胶质细胞瘤和 2 例混合性肿瘤）的 GEP（U133Plus2.0 芯片）及其与肿瘤细胞遗传学和组织病理学的关系。非监督和监督分析显示，低级别和高级别胶质瘤之间的 GEP 存在显著差异，最具鉴别力的基因包括参与细胞增殖、凋亡、DNA 修复和信号转导调节的基因。反过来，在多形性胶质母细胞瘤（GBM）中，根据 GEP 确定了 3 个肿瘤亚组，这些亚组与它们原始肿瘤细胞克隆的细胞遗传学特征密切相关：（i）EGFR 扩增，（ii）孤立的三体 7，和（iii）更复杂的核型。总之，我们的结果表明胶质瘤的 GEP 与肿瘤组织病理学之间存在明显的关联；此外，在 4 级星形细胞瘤中，GEP 与原始肿瘤细胞克隆的细胞遗传学特征显著相关。需要在更大系列的患者中进行进一步研究来证实我们的观察结果。
