Identification of molecular subtypes of glioblastoma by gene expression profiling

Identification of molecular subtypes of glioblastoma by gene expression profiling
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DOI:
10.1038/sj.onc.1206344
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发表时间:
2003-04-17
期刊:
影响因子:
8
通讯作者:
Nelson, SF
Nelson, SF
中科院分区:
医学1区
文献类型:
--
作者:
Mischel, PS;Shai, R;Nelson, SF

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近50%的胶质母细胞瘤(GBM)病例中存在表皮生长因子受体(EGFR)过表达,但其临床和生物学意义尚不清楚。我们已经使用Affytron高密度寡核苷酸阵列来证明EGFR过表达GBM(EGFR +)具有独特的全局基因转录谱。我们发现,90个基因的表达可以区分EGFR +和EGFR非表达(EGFR-)GBM,包括一些已知作为GBM生长/存活因子的基因。我们还发现了另外两种新的GBM分子亚型,其中一种的特征是染色体12 q13 -15上相邻基因的协调上调以及星形胶质细胞和少突胶质细胞基因的表达。这些结果定义了GBM的不同分子亚型,这在疾病分层以及GBM治疗策略的发现和评估中可能是重要的。
Epidermal growth factor receptor (EGFR) overexpression occurs in nearly 50% of cases of glioblastoma (GBM), but its clinical and biological implications are not well understood. We have used Affymetrix high-density oligonucleotide arrays to demonstrate that EGFR-over-expressing GBMs (EGFR +) have a distinct global gene transcriptional profile. We show that the expression of 90 genes can distinguish EGFR + from EGFR nonexpressing (EGFR-) GBMs, including a number of genes known to act as growth/survival factors for GBMs. We have also uncovered two additional novel molecular subtypes of GBMs, one of which is characterized by coordinate upregulation of contiguous genes on chromosome 12q13-15 and expression of both astrocytic and oligodendroglial genes. These results define distinct molecular subtypes of GBMs that may be important in disease stratification, and in the discovery and assessment of GBM treatment strategies.