Abstract
Schwannomas are benign tumors that arise sporadically or associated to the NF2 syndrome. The characteristic alteration in schwannomas is the loss of heterozygosity of 22q (up to 50%), where NF2 gene is located. Inactivating mutations of this gene have been found up to 66% of sporadic schwannomas and 33% of NF2-associated tumors. NF2 nonsense and frameshift mutations, both causing truncated proteins, are associated with more severe phenotypes. Merlin, the product of NF2 gene, belongs to the ERM family of proteins that connect the actin cytoskeleton with plasma membrane. Merlin functions as a tumor suppressor and is involved in cell-cell and cell-matrix interactions through an array of molecular pathways. Merlin over-expression can inhibit both cell proliferation and the transformation induced by oncogenes, and its down-regulation cause a lack in contact inhibition, leading to neoplastic transformation. Another oncogenic mechanism studied in schwannomas is the epigenetic hypermethylation of genic promoters. The study of epigenetic gene silencing in schwannomas has shown high frequencies of promoter hypermethylation in some well known cancer-related genes, and specifically on NF2 gene. There are many unknown aspects in the molecular biology of schwannomas. However, current knowledge and technical advances allows us to be optimistic about future perspectives.
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Martínez-Glez, V., Torres-Martín, M., Castresana, J.S., Lassaletta, L., Rey, J.A. (2012). Schwannomas: Role of Molecular Genetics and Epigenetic Mechanisms. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 7. Tumors of the Central Nervous System, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2894-3_24
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