Genetic alterations in glioblastoma multiforme

Book Section

Glioblastoma multiforme (GBM), or Grade IV astrocytoma, is one of the most common and malignant primary tumors of the central nervous system in adults [1]. Despite years of research and advances, the average survival after diagnosis remains about 12 months [1–4]. GBM tumors can be divided into two groups: primary and secondary. Primary GBM presents de novo as GBM with no preceding lower grade tumor, representing over 90% of GBM cases [5]. On the other hand, secondary GBM first presents as a lower grade glioma and is part of a progression of increasing grade of astrocytoma: World Health Organization (WHO) Grade II diffuse astrocytoma (often called low-grade glioma), WHO Grade III anaplastic astrocytoma, and WHO Grade IV glioblastoma [5]. WHO Grade I pilocytic astrocytomas are not thought to progress [6]. Despite a similar histopathology, primary and secondary GBM each comprise a distinct combination of genetic changes and tend to occur in distinct populations. Whereas primary GBM generally occurs in older patients, usually over 60 years old [3], secondary GBM tends to occur in middle-aged patients, of an average age of 45 years [3]. Because of these differences between primary and secondary GBM, it is entirely possible that treatments that are effective in one GBM patient population will be ineffective in others, and vice versa. The importance of understanding the genetic differences in GBM tumors from different patients is becoming increasingly clear, as genetic differences between tumors may more accurately predict prognosis than histological differences alone [7, 8]. Furthermore, because different GBM patients present with distinct combinations of genetic mutations, it is likely that therapies targeted to the specific genetic pathways that are altered in a patient's tumor will be the most efficacious way of treating this disease. However, due to the heterogeneous genome of GBM tumors, with different cells within one tumor having different mutations, tailored treatments targeting the multiple dysregulated oncogenic pathways in cancer cells of differing genotypes may achieve the most effective outcome. Identification of the genetic changes that occur in subsets of cells is critical to optimizing treatment for each patient. In this review, we focus on the genetic pathways identified as commonly altered in GBMs and the implications of changes in these pathways for prognosis and treatment.

Full Text

Duke Authors

Cited Authors

  • López, GY; Samsky, M; Jones, R; Adamson, C; Yan, H

Published Date

  • January 1, 2015

Book Title

  • Systems Biology of Cancer

Start / End Page

  • 323 - 344

International Standard Book Number 13 (ISBN-13)

  • 9780521493390

Digital Object Identifier (DOI)

  • 10.1017/9780511979811.022

Citation Source

  • Scopus