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  • Oncogenomics
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Identification of molecular subtypes of glioblastoma by gene expression profiling

Oncogene volume 22, pages 2361–2373 (2003)Cite this article

Abstract

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.

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Acknowledgements

We are grateful to Drs Charles Sawyers, Daniel Geschwind, William McBride, Harry Vinters and Jonathan Braun for their helpful comments on this manuscript. This work was supported by U01 CA88127 from the National Cancer Institute (SFN) and K08NS43147-01 from the National Institute of Neurological Disorders and Stroke, NIH (to PSM). PSM was also supported by an Accelerate Brain Cancer Cure Award, a Henry E Singleton Brain Tumor Fellowship, a generous donation from the Kevin Riley family to UCLA Comprehensive Brain Tumor Program and the Harry Allgauer Foundation through The Doris R Ullmann Fund for Brain Tumor Research Technologies. GC was supported by a postdoctoral fellowship from Korea Science & Engineering Foundation (KOSEF) (to GC). Tao Shi is a predoctoral trainee supported by the UCLA IGERT Bioinformatics Program funded by NSF DGE 9987641. Kan V Lu is supported by USHHS Institutional National Research Service Award #T32 CA09056.

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  1. Paul S Mischel and Ruty Shai: These authors contributed equally

Authors and Affiliations

  1. Department of Pathology, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Paul S Mischel, Kan V Lu, Gheeyoung Choe, David Seligson & Aarno Palotie

  2. Department of Human Genetics, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Ruty Shai, Tao Shi, Steve Horvath & Stanley F Nelson

  3. Department of Neurosurgery, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Thomas J Kremen & Linda M Liau

  4. Department of Neurology, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Timothy F Cloughesy

  5. Department of Biostatistics, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Tao Shi & Steve Horvath

  6. The Henry E Singleton Brain Tumor Program, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Paul S Mischel, Linda M Liau, Timothy F Cloughesy & Stanley F Nelson

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Correspondence to Paul S Mischel.

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Mischel, P., Shai, R., Shi, T. et al. Identification of molecular subtypes of glioblastoma by gene expression profiling. Oncogene 22, 2361–2373 (2003). https://doi.org/10.1038/sj.onc.1206344

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