González-Tablas María, Arandia Daniel, Jara-Acevedo María, Otero Álvaro, Vital Ana-Luisa, Prieto Carlos, González-Garcia Nerea, Nieto-Librero Ana Belén, Tao Herminio, Pascual Daniel, Ruiz Laura, Sousa Pablo, Galindo-Villardón Purificación, Orfao Alberto, Tabernero María Dolores
Instituto de Investigación Biomédica de Salamanca, IBSAL-University Hospital of Salamanca, 37007 Salamanca, Spain.
Centre for Cancer Research (CIC-IBMCC, CSIC/USAL, IBSAL) and Department of Medicine, University of Salamanca, 37007 Salamanca, Spain.
Cancers (Basel). 2020 Jan 17;12(1):231. doi: 10.3390/cancers12010231.
The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial.
We investigated the RNA gene expression profile of epidermal growth factor receptor (), cyclin-dependent kinase 4 (), murine doble minute 4 (), and platelet derived growth factor receptor alpha () in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in and were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied.
At the RNA level, was the most frequently overexpressed gene (90%) followed by (58%) and (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with gene expression levels. In turn, intragenic deletions were found in 39 patients (47%), including (46%) in association with (4%), (2%) or other deletions (3%) and deletion of exons 8-9 was found in only two tumors (2%).
Overall, none of the gene expression profiles and/or intragenic deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.
在多形性胶质母细胞瘤（GBM）中反复扩增的基因表达谱的预后影响仍存在争议。
我们调查了83例原发性GBM肿瘤与42例正常脑组织样本中表皮生长因子受体（EGFR）、细胞周期蛋白依赖性激酶4（CDK4）、鼠双微体4（MDM4）和血小板衍生生长因子受体α（PDGFRA）的RNA基因表达谱。对这四个基因进行间期荧光原位杂交（iFISH）分析，并在DNA水平上同时评估EGFR和MDM4的基因内缺失情况。作为验证队列，我们还研究了来自10个不同GBM患者系列的293个样本的公开可用RNA基因表达数据。
在RNA水平上，EGFR是最常过度表达的基因（90%），其次是MDM4（58%）和CDK4（58%）。7号染色体拷贝数改变，即三体性（49%）和多体性（44%），与EGFR基因表达水平无明显关联。反过来，在39例患者（47%）中发现了EGFR基因内缺失，其中包括与CDK4缺失（4%）、MDM4缺失（2%）或其他EGFR缺失（3%）相关的缺失，并且仅在两个肿瘤（2%）中发现了外显子8 - 9的MDM4缺失。
总体而言，基因表达谱和/或基因内EGFR缺失均未显示对GBM的总生存期有显著影响，这支持了该疾病的其他尚未阐明的特征可能在GBM中发挥更相关的预后作用这一观点。
