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.

Deletions of the long arm of chromosome 10 in progression of follicular thyroid tumors

“…LOH on the long arm of chromosome 10 has also been found in the progression of other tumor types, e.g., glioblastomas (Leon et al 1994), malignant meningiomas (Rempel et al 1993), malignant melanomas (Isshiki et al 1993), and bladder carcinomas (Wang et al 1994). In an earlier paper, we touched upon an interesting finding of an aggressive follicular thyroid carcinoma in a young girl with a constitutional ring chromosome, most likely lacking genetic material at the distal part of chromosome lOq (Sparkes et al 1978;Tommerup and Lothe 1992).…”

Human neurotropic polyomavirus, JCV, and its role in carcinogenesis

“…Hematoxylin and eosin staining revealed interdigitating spindle cells and expression of the neuronal marker protein, S-100 (Figure 2, Panels g and h, respectively), consistent with malignant peripheral nerve sheath tumors (mpnst) (Gordon et al, unpublished observations). Interestingly, the incidence of pituitary tumors and mpnst mimics that observed in the human population in that pituitary tumors have a relatively high incidence as they account for 8-10% of all intracranial neoplasms, while mpnst are fairly uncommon (Leon et al, 1994;Woodruff et al, 2000). Observations similar to those made in the mouse medulloblastoma tumors, namely the expression of T-antigen in the tumor tissue and its association with p53 and pRb, have been made in the pituitary tumors and mpnst as well.…”

Molecular genetics of meningiomas

“…11,26,42,47,79,89,91 An NF2-associated meningioma is relatively rare, however, because the majority of these lesions occur as isolated, sporadic tumors. Nevertheless, deletions of chromosome 22 are found in all NF2-associated meningiomas, and in 54 to 78% of sporadic meningiomas.…”