Magic but treatable? Tumours due to loss of Merlin

Alterations in the NF2 gene coding for merlin cause all tumours that occur in patients suffering from neurofibromatosis type 2, all spontaneous schwannomas and the majority of meningiomas. Thus merlin's tumours are quite frequent and also numerous when inherited as part of meurofibromatosis type 2. Tumours caused by mutations in the NF2 gene are benign and thus do not respond to classical chemotherapy. Surgery and radiosurgery are only local therapies and the patients frequently require multiple treatments. This highlights the medical need to understand how merlin loss results in tumourigenesis and the need to find new systemic therapies. The benign, and therefore genetically stable and homogenous character of the tumours allows establishment of meaningful tumour models. This brings about the rather unique opportunity to both analyse the consequences of the gene defect and identify new therapeutic targets. In this review, I will first describe the phenotypes associated with merlin mutations and consider differential diagnosis, in particular Schwannomatosis, for which a gene defect has been described recently. Existing therapeutic options, surgery and radiosurgery, including new data on the latter will be reviewed. Finally, I will discuss how loss of merlin leads to tumourigenesis in order to understand the rationale for emerging new therapeutic targets.