Glioblastoma is an aggressive type of brain cancer originating from glial cells, which are supportive cells in the brain. It is considered the most common and most aggressive primary brain tumor in adults. These tumors grow and spread rapidly, often invading surrounding healthy brain tissue. Despite its challenging nature, glioblastoma is rarely inherited, with the vast majority of cases occurring without a family history of the disease.
Glioblastoma: Primarily Sporadic
The development of glioblastoma typically arises from random genetic changes that occur throughout a person’s lifetime, rather than being passed down through generations. These acquired mutations are known as somatic mutations, meaning they are present only in the tumor cells and not in every cell of the body. Most glioblastoma cases are sporadic, indicating they develop without a clear hereditary cause.
The precise reasons for these sporadic mutations are not fully understood, but they are thought to accumulate over time due to factors like normal cell division processes. Unlike inherited mutations, which are present from birth, somatic mutations occur during a person’s life and contribute to the uncontrolled cell growth characteristic of cancer.
Rare Genetic Syndromes Linked to Glioblastoma
While most glioblastomas are sporadic, a small percentage of cases are associated with inherited genetic conditions. These rare cancer predisposition syndromes significantly increase an individual’s risk of developing glioblastoma or other brain tumors.
Neurofibromatosis Type 1 (NF1) is an inherited condition that raises the risk of developing various tumors, including glioblastoma. It results from mutations in the NF1 gene, which typically regulates cell growth. Individuals with NF1 have a considerably higher risk of brain tumors, with glioblastomas most often observed in adults with the condition.
Li-Fraumeni Syndrome (LFS) is another rare inherited disorder linked to an increased cancer risk, including glioblastoma. This syndrome is caused by germline mutations in the TP53 tumor suppressor gene, which plays a role in preventing tumor formation. Patients with LFS can develop glioblastoma at a younger age compared to sporadic cases, and they are also prone to other cancer types like sarcomas and breast cancer.
Turcot Syndrome is characterized by the presence of multiple colon polyps and an increased risk of brain tumors, including glioblastoma. This condition can be inherited, with specific gene mutations (such as MLH1 and PMS2) being associated with glioblastoma development in affected families. The type of brain tumor in Turcot Syndrome can depend on the underlying genetic mutation.
Constitutional Mismatch Repair Deficiency (CMMRD) is a rare autosomal recessive syndrome caused by inherited mutations in mismatch repair (MMR) genes. Individuals with CMMRD have a high risk of developing various cancers, including malignant brain tumors like glioblastoma, often at an early age. Glioblastomas associated with CMMRD may present unique characteristics compared to other pediatric high-grade gliomas.
Assessing Family Risk and Genetic Counseling
For individuals concerned about a potential hereditary link to glioblastoma in their family, genetic counseling can provide valuable guidance. Genetic counseling involves a detailed review of personal and family medical history to assess the likelihood of an inherited predisposition. A genetic counselor can discuss whether genetic testing is appropriate, explaining its benefits and limitations.
Genetic testing can be performed on blood or saliva samples to identify inherited gene mutations that may increase cancer susceptibility. The decision to pursue genetic testing is a personal one, typically considered when there are multiple family members with brain tumors, very early-onset glioblastoma, or other cancers commonly associated with known genetic syndromes.