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The Korean Journal of Pathology 2002;36(5): 328-337.
Molecular Subtypes of Primary Glioblastoma Identified by Gene Expression Profiling.
Ghee Young Choe, S Mischel Paul
1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. gychoe@plaza.snu.ac.kr
2Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, California, U.S.A.
BACKGROUND: The over-expression of the epidermal growth factor receptor (EGFR) occurs in nearly 50% of primary glioblastoma multiforme (GBM). Disruption of multiple signaling pathways is a critical factor in regulating the biological and clinical behavior of GBMs. In the future, therapy that specifically targets these disrupted pathways may represent the best potential treatment for patients with GBM. Large scale gene expression profiling provides a powerful approach to identify these disrupted genetic pathways and to uncover previously unknown molecular subtypes. METHODS: We used 13 cases of primary GBM biopsy samples obtained from untreated patients and Affymetrix high-density oligonucleotide arrays to identify novel subsets of primary GBMs. RESULTS: We showed that the expression of 90 genes differentiate EGFR+ from EGFR non-expressing (EGFR-) de novo GBMs, including expression of a number of potentially targetable molecules that act as growth/survival factors for GBMs. We also demonstrated the presence of two additional molecular subtypes of primary GBMs, including one characterized by the coordinate upregulation of contiguous genes on chromosome 12q13-15, which has a distinct global gene expression profile and expresses both astrocytic and oligodendroglial genes. CONCLUSION: We have shown that there are EGFR+ primary GBMs, GBMs with coordinate upregulation of genes on chromosome 12q13-15, and primary GBMs lacking either alteration. Moreover, they have distinct transcriptional profiles. Our findings strongly suggest that the three GBMs are biologically different tumor types, despite their identical microscopic appearance, and provide an important first step in developing a molecular taxonomy of GBMs.
Key Words: Glioblastoma; Genes; erbB-1; Gene Expression Profiling; Oligonucleotide Array Sequence Analysis
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