‘NF2: State of the Art’ got off to an exciting start this morning. Gareth Evans opened the day with a talk on NF2 genetics, and speculated that though the generation of merlin protein from the NF2 gene is truncated when there is a nonsense mutation, nevertheless some protein must be made that is able to bind to ‘healthy’ NF2 protein, resulting in tumor growth. A trio of talks from Andi McClatchey, Helen Morrison and Filippo Giancotti focused on the cellular and molecular basis of NF2. These reviewed mechanisms of cell growth regulation by different functional domains and forms of merlin protein at the cell membrane and also in the nucleus, opening up a diverse array of candidate drug targets for NF2 drug therapies. In an intriguing presentation, Anat Stemmer-Rachamimov reported data from an examination of tumorlets taken from NF2 patients. Tumorlets are tiny tumors embedded in the nerve and often identified only at time of autopsy, but are believed to be the predecessor from which full blown NF2 vestibular schwannomas develop. A comparison of tumorlets and vestibular schwannomas from NF2 patients and seen quite a difference in genes expressed between the two tumor types. This may help unravel and separate out the signals that trigger the initiation, and then the advancement of growth, of NF2 tumors.
Switching late morning to NF2 tumor management presentations, Bill Slattery and Michel Kalamarides presented natural history studies from the United States and France, respectively. Natural history studies provide an opportunity to follow the natural progression of NF2 tumor growth etc. so that appropriate clinical management strategies can be developed. There were a number of common features, notably the left and right vestibular schwannoma in a person will usually have independent growth rates. There was discussion about spinal tumors and whether these are likely to grow and require treatment. A percentage of patients will have spinal tumors requiring surgery often because of cord compression. Certain spinal tumors such as ependymomas may be largely inactive but potentially could be a concern in older adults. Dr. Karajannis and John Golfinos focused on meningiomas in NF2 patients. These are likely to be more problematic than sporadic meningiomas, should be very closely monitored, and when operated on the whole brain picture needs to be understood to consider which meningioma areas are likely to require surgery next.
More to follow – please follow us on Twitter for ‘real time’ updates from the meeting!
