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Clonality of multiple meningiomas
A P Stangl1, R Wellenreuther, D Lenartz
1Institute of Neuropathology and Neurosurgery Clinic, University Hospital of Bonn, Germany.
Abstract:
A significant number of patients with meningiomas develop multiple tumors without anatomical bridges. To understand the mechanism by which multiple meningiomas arise, the authors analyzed DNA from 39 multiple meningiomas in 12 patients to locate alterations in the neurofibromatosis type 2 (NF2) gene. This gene has been shown to be inactivated in meningiomas. No patient in our series had a family history of meningiomas or NF2. All tumors were investigated by single-strand conformation polymorphism analysis of the entire coding region of the NF2 gene and by direct DNA sequencing of altered fragments. The DNA from meningiomas in 10 patients carried NF2 gene mutations. In six of the 10 patients with NF2 mutations, all tumors in the respective individual exhibited the identical DNA alteration in the NF2 gene, thus indicating clonal origin. All four patients with more than two lesions had clonal meningiomas and four patients with two meningiomas each carried different mutations in their tumors. Analysis of constitutional DNA revealed a wild-type NF2 sequence in all 12 patients, thus excluding a forme fruste of NF2 in these cases. Our data demonstrate that the majority of multiple meningiomas with NF2 gene mutations are of somatic and clonal origin. Spread of tumor cells via the cerebrospinal fluid is the most likely mechanism to account for the development of these multiple meningiomas.
Insights
Most multiple meningiomas stem from a single cell's mutation in the neurofibromatosis type 2 (NF2) gene. Tumor cells likely spread through cerebrospinal fluid to form new, clonal meningiomas.
Area of Science:
- Oncology
- Genetics
- Neurosurgery
Background:
- Multiple meningiomas can develop without clear anatomical connections.
- The neurofibromatosis type 2 (NF2) gene is frequently inactivated in meningiomas.
Purpose of the Study:
- To investigate the genetic origin of multiple meningiomas.
- To determine if multiple meningiomas arise from a single clone or independent events.
Main Methods:
- DNA analysis of 39 meningiomas from 12 patients.
- Single-strand conformation polymorphism and DNA sequencing of the NF2 gene.
- Analysis of constitutional DNA to exclude inherited NF2 mutations.
Main Results:
- NF2 gene mutations were found in 10 of 12 patients.
- In 6 patients, all tumors shared identical NF2 mutations, indicating clonal origin.
- Four patients with multiple lesions had clonal meningiomas; two had distinct mutations.
Conclusions:
- The majority of multiple meningiomas with NF2 mutations are of somatic and clonal origin.
- Spread of tumor cells via cerebrospinal fluid is the likely mechanism for multiple tumor development.