Causes

A glioblastoma can develop primarily (mostly elderly patients), but also secondarily through progressive growth (progression) of a WHO Grade III astrocytoma (mostly middle-aged patients). Astrocytomas develop from certain glial cells, the astrocytes, and, like glioblastomas, belong to the group of gliomas. The role of genetic factors in the development of brain tumors has become increasingly important in recent years.

Patients with secondary glioblastomas have as their main distinguishing feature a change in the protein p53 (p53 mutation), which controls the cell cycle (tumor suppressor), and a loss of genes (allele loss) on chromosome 17. In addition, they are 10 to 20 years younger than patients with primary glioblastoma, who typically have EGF receptor gene amplification (amplification) or excessive production (overexpression) of the EGF receptor. The EGF receptor serves as a docking site for the epidermal growth factor, which acts as a signal molecule in the cell cycle.Glioblastomas are genetically very different (heterogeneous) and have a loss of one gene (deletions) in about 20% and gene duplications in about 50%.

The most common finding is a loss of a gene on chromosome 10 in three quarters of cases. For the majority of brain tumors, however, genetic factors play no role. Environmental factors also play only a minor role.

An example of an influencing environmental factor is the vinyl chloride in the plastic PVC. A hereditary genetic factor can be observed in the rare hereditary diseases Li-Fraumeni syndrome and Turcot syndrome. Here, glioblastomas occur more frequently in families.

The causes of glioblastoma are not fully understood. The vast majority of glioblastomas develop spontaneously, i.e. by chance. However, high radiation exposure has been identified as a risk factor.

There are also rare genetic diseases in which those affected generally have an increased risk of tumors, such as Li-Fraumeni syndrome. Diseases of this type are also considered a risk factor for developing glioblastoma. In addition, it is not uncommon for grade 3 brain tumors to become more malignant in the course of the disease, which can lead to the development of a glioblastoma (grade 4).

This process is called malignant progression. Based on another brain tumor, a glioblastoma can also develop under therapy. In this case, the term secondary glioblastoma is used in medical terminology.