A survey of glioblastoma genomic amplifications and deletions
A survey of glioblastoma genomic amplifications and deletions
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DOI：
10.1007/s11060-009-9959-4
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发表时间：
2010-01-01
影响因子：
3.9
通讯作者：
Riggins, Gregory J.
中科院分区：
文献类型：
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作者：
Rao, Shailaja K.;Edwards, Jennifer;Riggins, Gregory J.
多形性胶质母细胞瘤（GBM）是一种恶性脑癌，在积累基因组DNA损伤后发展，通常包括基因扩增和/或缺失。这些拷贝数的变化可能是脑肿瘤发展的关键步骤。为了评估胶质母细胞瘤基因组拷贝数的变化，我们确定了31个GBM的全基因组拷贝数改变。使用Illumina Bead Arrays测定22个GBM，并对8个GBM细胞系和一个初级样品使用数字核型分析。我们在所有31个样本中观察到的常见扩增是GLI/CDK 4（22.6%）、MDM 2（12.9%）和PIK 3C 2B/MDM 4（12.9%）。在22例GBM肿瘤中，EGFR在22.7%的手术活检中扩增。最常见的同源性缺失区域包含CDKN 2A/CDKN 2B（p15和p16），发生在29%的病例中。这些数据被汇编并与456例GBM的已发表阵列CGH研究进行比较。将我们的Illumina数据与已发表的研究进行汇总，得出这些平均扩增率：EGFR-35.7%，GLI/CDK 4 - 13.4%，MDM 2 - 9.2%，PIK 3C 2B/MDM 4 - 7.7%和PDGFRA-7.7%。CDKN 2A/CDKN 2B基因缺失率为46.4%。这项研究提供了胶质母细胞瘤患者人群中扩增和缺失的更大评估，并表明几种不同的拷贝数技术可以产生类似的结果。已知参与GBM肿瘤形成的主要途径，如p53控制、生长信号传导和细胞周期控制，都由关键途径基因的扩增或缺失代表。这些信息对于制定胶质母细胞瘤的靶向治疗和计划基因组研究具有潜在的重要性。
Glioblastoma Multiforme (GBM) is a malignant brain cancer that develops after accumulating genomic DNA damage that often includes gene amplifications and/or deletions. These copy number changes can be a critical step in brain tumor development. To evaluate glioblastoma genomic copy number changes, we determined the genome-wide copy number alterations in 31 GBMs. Illumina Bead Arrays were used to assay 22 GBMs and Digital Karyotyping was used on 8 GBM cell lines and one primary sample. The common amplifications we observed for all 31 samples was GLI/CDK4 (22.6%), MDM2 (12.9%) and PIK3C2B/MDM4 (12.9%). In the 22 GBM tumors, EGFR was amplified in 22.7% of surgical biopsies. The most common homozygously deleted region contained CDKN2A/CDKN2B (p15 and p16) occurring in 29% of cases. This data was compiled and compared to published array CGH studies of 456 cases of GBMs. Pooling our Illumina data with published studies yielded these average amplification rates: EGFR-35.7%, GLI/CDK4-13.4%, MDM2-9.2%, PIK3C2B/MDM4-7.7%, and PDGFRA-7.7%. The CDKN2A/CDKN2B locus was deleted in 46.4% of the combined cases. This study provides a larger assessment of amplifications and deletions in glioblastoma patient populations and shows that several different copy number technologies can produce similar results. The main pathways known to be involved in GBM tumor formation such as p53 control, growth signaling, and cell cycle control are all represented by amplifications or deletions of critical pathway genes. This information is potentially important for formulating targeted therapy in glioblastoma and for planning genomic studies.