胶质母细胞瘤（GBM）是中枢神经系统最常见的肿瘤，其异质性对治疗构成了挑战。本研究考察了涉及PDGFRA，KIT和KDR基因扩增（GA）在4q12位点的肿瘤异质性，并与临床参数进行了关联。利用FISH技术检测到的22例GBM患者4q12扩增子探针的标志物，观察了异质性或均质性的共扩增模式、质谱特征以及用于扩增信号团簇进行染色体定位。其中，16例患者（45.5%）PDGFRA，KIT和KDR基因均表现为均质性扩增，另有PDGFRA和KDR基因扩增（22.7%），或仅PDGFRA（4.6%）的扩增情况；6例患者（13.6%）出现不均质性扩增情况，其中包括PDGFRA、KIT和KDR基因共同扩增，或PDGFRA和KDR基因扩增（9.1%），或PDGFRA和KIT基因扩增（4.6%）。在6例肿瘤中（27.3%），扩增观察到局部肿瘤区域，而在其余的16例肿瘤中（72.7%），扩增分布于肿瘤组织的各个区域。扩增普遍表达为双倍体和均质染色区域。PDGFRA，KIT和KDR三个基因的共扩增、年龄≥60岁以及完全切除的肿瘤与不良预后有显著相关。FISH技术在分子异质性的详细解释方面具有很好的效果。研究发现在GBM中涉及4q12致癌基因的扩增模式比以往所描述的更为多样化，因此显示在设计更有效的治疗方案时必须考虑到肿瘤的复杂异质性。©2023。这是美国政府的工作，不受美国版权法保护；可能适用外国版权保护。

Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes - PDGFRA and KDR (13.6%), or GA for all three and for only one gene - PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.