Mischel Paul S, Shai Ruty, Shi Tao, Horvath Steve, Lu Kan V, Choe Gheeyoung, Seligson David, Kremen Thomas J, Palotie Aarno, Liau Linda M, Cloughesy Timothy F, Nelson Stanley F
Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Oncogene. 2003 Apr 17;22(15):2361-73. doi: 10.1038/sj.onc.1206344.
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-overexpressing 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.
表皮生长因子受体（EGFR）过表达在近50%的胶质母细胞瘤（GBM）病例中出现，但其临床和生物学意义尚未完全明确。我们使用Affymetrix高密度寡核苷酸阵列证明，EGFR过表达的GBM（EGFR+）具有独特的全基因组转录谱。我们发现90个基因的表达可区分EGFR+与不表达EGFR（EGFR-）的GBM，其中包括一些已知作为GBM生长/存活因子的基因。我们还发现了GBM的另外两种新的分子亚型，其中一种的特征是12q13 - 15染色体上相邻基因的协同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，这可能对疾病分层以及GBM治疗策略的发现和评估具有重要意义。
