Elsevier

Cancer Genetics

Volume 208, Issue 4, April 2015, Pages 107-114
Cancer Genetics

Review article
Germline and somatic mutations in meningiomas

https://doi.org/10.1016/j.cancergen.2015.02.003Get rights and content

Meningiomas arise from the arachnoid layer of the meninges that surround the brain and spine. They account for over one third of all primary central nervous system tumors in adults and confer a significant risk of location-dependent morbidity due to compression or displacement. A significant increase in risk of meningiomas is associated with neurofibromatosis type 2 (NF2) disease through mutation of the NF2 gene. In addition, approximately 5% of individuals with schwannomatosis disease develop meningiomas, through mutation of the SWI/SNF chromatin remodeling complex subunit, SMARCB1. Recently, a second SWI/SNF complex subunit, SMARCE1, was identified as a cause of clear cell meningiomas, indicating a wider role for this complex in meningioma disease. The sonic hedgehog (SHH)-GLI1 signaling pathway gene, SUFU, has also been identified as the cause of hereditary multiple meningiomas in a large Finnish family. The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas. This review describes the known meningioma predisposition genes and their links to the recently identified somatic mutations.

Section snippets

NF2

Germline mutation of the NF2 gene is the most commonly identified genetic risk factor for multiple meningioma disease. Multiple meningiomas often occur as part of the NF2 tumor suppressor syndrome. Germline NF2 mutations are detectable in over 90% of all cases of nonmosaic NF2 disease and confer a significant risk of meningiomas, with approximately 50% of people with NF2 developing at least one intracranial meningioma during their lifetime. The presence of intracranial meningiomas in NF2 is

Conclusion

Meningiomas are a diverse group of tumors with varied histology and growth patterns. The heterogeneity in germline and somatic mutations indicates a complex network of pathway interactions involving the SHH-GLI1 and AKT1-MTOR signaling pathways, which require further investigation. Further studies are also needed to understand the role of chromatin remodeling factors in these pathways and how the meningioma-associated mutations lead to tumor formation. Categorization by of meningiomas by

Acknowledgments

M.J.S. is currently funded by a Drug Discovery Initiative grant (2014A-05-016) and a Schwannomatosis Award (2014-02-001) from the Children's Tumor Foundation.

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