Meningiomas are common brain tumors, often found incidentally during imaging. Their origins and link to genetic makeup are common questions. Understanding their genetic aspects helps clarify development and potential inherited risks.
What Are Meningiomas?
Meningiomas are tumors developing from the meninges, the protective membranes covering the brain and spinal cord. They are the most common primary brain tumor in adults, accounting for approximately 37.6% of such tumors.
Most meningiomas are slow-growing and benign (Grade I), but some can be atypical (Grade II) or malignant (Grade III). Their growth rate and location influence symptoms like headaches, seizures, or vision changes if they press on nearby structures. About 1% of people may develop a meningioma in their lifetime.
The Genetic Connection
Meningiomas can have a genetic component, manifesting as inherited predispositions or sporadic mutations. A small percentage are linked to inherited genetic syndromes, where an individual is born with a genetic alteration increasing their lifetime risk.
The vast majority, however, arise from sporadic (somatic) mutations. These mutations occur within tumor cells during a person’s lifetime and are not passed down. Researchers have found genetic changes on chromosome 22 in many sporadic meningiomas.
Key Genes Involved
For inherited predisposition, the NF2 gene (Neurofibromin 2) is key. Mutations in this gene cause Neurofibromatosis Type 2 (NF2), a rare genetic condition. Individuals with NF2 often develop multiple meningiomas due to impaired merlin function. Merlin is a tumor suppressor protein, and its loss of function can lead to uncontrolled cell growth.
For sporadic meningiomas, other genes frequently have mutations, including TRAF7, KLF4, AKT1, and SMO. TRAF7 mutations are present in nearly a quarter of all meningiomas, sometimes co-occurring with KLF4 mutations. Mutated KLF4 is commonly seen in Grade I meningiomas.
AKT1 mutations can activate cell growth pathways and are found in a subset of Grade I meningiomas, often alongside TRAF7 mutations. SMO mutations, which activate the Hedgehog signaling pathway, are identified in about 5% of non-NF2 mutant meningiomas. BAP1 is a tumor suppressor gene identified in a rare subset of aggressive meningiomas.
Implications of Genetic Insights
Understanding the genetic basis of meningiomas is important for individuals and families. Genetic knowledge aids in assessing risk, especially for those with a family history or features suggesting inherited syndromes like NF2. For example, a parent with NF2 has a 50% chance of passing the mutated gene to their children, helping identify individuals for closer monitoring.
Genetic counseling guides individuals and families through these complexities. A genetic counselor reviews family medical history and discusses genetic testing to determine if a gene variant contributes to a cancer pattern. This helps individuals understand risks and make informed health decisions.
Genetic research is also advancing personalized medicine for meningioma treatment. Studies explore how gene expression patterns can predict tumor behavior and response to therapies, potentially leading to more tailored strategies.