Genetic Aberrations in Human Brain Tumors

Abstract

Over the last decade, much has been learned about the genetic changes that occur in human neoplasia and how they contribute to the neoplastic state. Oncogenes and tumor suppressor genes have been identified, and many powerful molecular genetic techniques have emerged. Brain tumors have been intensively studied as part of this process. Specific and recurring genetic alterations have been identified and are associated with specific tumor types. In astrocytomas, for example, losses of genetic material on chromosomes 10 and 17 and amplification of the epidermal growth factor receptor gene seem important in pathogenesis, with the loss of chromosome 10 and the amplification of epidermal growth factor receptor being strongly associated with glioblastoma multiforme. Meningiomas, on the other hand, have usually lost part or all of chromosome 22. Brain tumors also express growth factors and growth factor receptors that may be important in promoting tumor growth and angiogenesis. These include epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor, the fibroblast growth factors, and vascular endothelial growth factor. In this article, we review the genetic aberrations that occur in the major types of brain tumors, including glial tumors, meningiomas, acoustic neuromas, medulloblastomas, primitive neuroectodermal tumors, and pituitary tumors. Wherever possible, clinical correlations have been made concerning the prognostic and therapeutic implications of specific aberrations. We also provide some background about the cytogenetic and molecular genetic techniques that have contributed to the description and understanding of these alterations and speculate as to some clinical and basic science issues that might be explored in the future.

Correlation between localization, age, and chromosomal imbalances in ependymal tumours as detected by CGH

“…Although one study reported resemblance at the molecular genetic level between ETs and astrocytic and oligodendroglial tumours (ATs and OTs)9, others reported that aberrations involved in the oncogenesis of ATs were rarely detected in ETs1, 4, 5, 19. OTs very frequently show loss of 1p and 19q8, 20–23.…”

Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization

“…evolution of gliomas and is important for the planning of rational therapeutic approaches at the molecular level. Most studies of this phenomenon in gliomas have focused on astrocytic tumors, and genetic models for tumor progression have been suggested (for reviews see 1,7,15,16,18,24 ). Malignant progression in oligodendroglial tumors, however, is still poorly understood, partly because techniques that have been used only reveal information about the region or gene of interest.…”

“…Malignant progression in oligodendroglial tumors, however, is still poorly understood, partly because techniques that have been used only reveal information about the region or gene of interest. Analysis has revealed that LOH at chromosomes 1p and 19q is an early event in the oncogenesis of these tumors (for reviews see 1,6,7,15 ). Additionally, it has been proposed that malignant progression in oligodendroglial tumors might be accompanied by losses of genetic material on chromosomes 9p and 10, and EGFR amplification.…”

Gains of chromosome 22 by fluorescence in situ hybridization in the context of an hyperdiploid karyotype are associated with aggressive clinical features in meningioma patients

“…In the past two decades, there has been an increasing number of studies devoted to the analysis of the cytogenetic characteristics of meningiomas 16–27. Many different genetic abnormalities have been identified in these tumors, those involving chromosome 22 such as monosomy 22/deletion of 22q being the most frequent ones 17, 28–30.…”