What causes brain tumors


Epidemiology studies have not indicated any particular factor (viral, chemical or traumatic) that What causes brain tumors in humans, although a range of cerebral tumours can be induced in ani- mals experimentally. There is no genetic predis-position but chromosome abnormalities have been noted in many CNS tumours . Neurofibromatosis type 1 (NF1), previously known as von Recklinghausen’s disease, occurs with an approximate frequency of 1 in 4000 live births. It is inherited as an autosomal dominant pattern and there is a high spontaneous mutation rate. NF1 is associated with a variety of central and peripheral nervous system tumours. An optic nerve glioma is the most common CNS tu- mour associated with NF1, occurring in about 15% of those affected. Less commonly low-grade glioma of the hypothalamus, cerebellum, brain- stem or spinal cord may occur. Peripheral neu- rofibromas are the hallmark of NF1 . Neurofibromas of the spinal roots are a common feature of NF1 (Chapter 15). The gene causing NF1 is located on the long arm of chromosome 17 (17q 11.2). Neurofibromatosis type 2 (NF2), previously known as central neurofibromatosis, is an auto- somal dominant disorder which, beyond a few superficial similarities, is phenotypically and genetically distinct from NF1. It has an incidence of approximately 1 in 100000 live births. The hall- mark of NF2 is bilateral acoustic (vestibular) schwannomas, but patients with NF2 have an in- creased risk of other intracranial schwannomas, multiple meningiomas (both cranial and spinal) and gliomas. The NF2 gene locus is sited on the long arm of chromosome 22 (22q 11.2) .

There is no specific evidence linking CNS tu- mours to environmental carcinogens, although many chemicals, especially ethyl and methyl nitrosourea and anthracene derivatives, show carcinogenic activity in animals and produce CNS tumours. Viral induction of brain tumours has been used in animal models but there is no firm evidence for viral aetiology in humans. Ahuman polyoma JC virus injected into primates produces tumours similar to human astrocytomas after an 18-month incubation period. This type of ‘slow virus’ effect may account for some of the problems of isolat- ing viruses from human tumours.

the identification of a variety of alterations in the genome of the tumour cell, including those of brain tumours. The present concept of oncogene- sis involves both the addition of oncogenes to the genome and the loss of the normally occurring tumour suppressor genes. Transformation (spon- taneous or induced) is a multistep process requir- ing both initiation and promotion. Oncogenes encode proteins that participate in the signal transduction and second messenger systems that modulate cell metabolism and proliferation. These proteins include both growth factors and growth factor receptors such as epidermal growth factor receptor, platelet-derived growth factor, tryosine-specific protein kinases and guanine-binding proteins. Tumour suppressor genes are normally pre- sent in the genome and act as a ‘brake’ on cell transformation. Mutations in the p53 tumour suppressor gene on chromosome 17 are the most common gene alteration found to date in tu- mours and have been shown to occur in both as- trocytomas and meningiomas. The Li–Fraumeni syndrome is due to a germ line mutation in the p53 gene with the development of numerous cancers including gliomas, ependymomas and medulloblastomas.

Although immunosuppression is known to in- crease markedly the risk of primary lymphoma

Viral induction of brain tumours has been used in animal models but there is no firm evidence for viral aetiology in humans. Ahuman polyoma JC virus injected into primates produces tumours similar to human astrocytomas after an 18-month incubation period. This type of ‘slow virus’ effect may account for some of the problems of isolat- ing viruses from human tumours. Although immunosuppression is known to in- crease markedly the risk of primary lymphoma of the brain, particularly in transplant recipients, there is not the corresponding increased inci- dence of gliomas. At present there is considerable conjecture re- garding the role of other possible aetiological agents, including trauma, electromagnetic radia- tion and organic solvents but, as yet, there is no the identification of a variety of alterations in the genome of the tumour cell, including those of brain tumours. The present concept of oncogene- sis involves both the addition of oncogenes to the genome and the loss of the normally occurring tumour suppressor genes. Transformation (spon- taneous or induced) is a multistep process requir- ing both initiation and promotion. Oncogenes encode proteins that participate in the signal transduction and second messenger systems that modulate cell metabolism and proliferation. These proteins include both growth factors and growth factor receptors such as epidermal growth factor receptor, platelet-derived growth factor, tryosine-specific protein kinases and guanine-binding proteins. Tumour suppressor genes are normally pre- sent in the genome and act as a ‘brake’ on cell transformation. Mutations in the p53 tumour suppressor gene on chromosome 17 are the most common gene alteration found to date in tu- mours and have been shown to occur in both as- trocytomas and meningiomas. The Li–Fraumeni syndrome is due to a germ line mutation in the p53 gene with the development of numerous cancers including gliomas, ependymomas and medulloblastomas.