Astrocytic Gliomas: Characterization on a Molecular Genetic Basis

Abstract

Astrocytic tumors are the most common primary human central nervous system tumors. Histopathological parameters have been employed to distinguish four grades of malignancy: pilocytic astrocytoma (WHO grade I), astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III), and glioblastoma multiforme (GBM; WHO grade IV; Kleihues et al. 1993). While classical histopathological methods have not been able to characterize pathogenic factors contributing to tumor formation in the brain, molecular analyses have revealed frequent chromosomal alterations that may indicate specific molecular genetic mechanisms. The involvement of oncogenes and tumor suppressor genes in neoplastic disorders has now been firmly established (Bishop 1991; Marshall 1991). Several characteristic genomic alterations have been identified in astrocytic gliomas. Loss of portions of the short arm of chromosome 17 is observed in grade II and III astrocytoma and GBM (El-Azouzi et al. 1989; Fults et al. 1989; James et al. 1989; von Deimling et al. 1992), while loss of chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are essentially restricted to GBM (Libermann et al. 1984; Bigner et al. 1988; James et al. 1988; Fujimoto et al. 1989; Fults et al. 1990; Watanabe et al. 1990; von Deimling et al. 1992).