Expression analysis of genes lying in the NF1 microdeletion interval points to four candidate modifiers for neurofibroma formation.

The hallmark of neurofibromatosis type 1 (NF1) are multiple dermal neurofibromas. They show high inter- and intrafamilial variability for which the influence of modifying genes is discussed. NF1 patients presenting microdeletions spanning NF1 and several contiguous genes have an earlier onset and higher number of dermal neurofibromas than classical NF1 patients, pointing to one of the deleted genes as modifier. Expression analysis of 13 genes of the microdeletion region in dermal neurofibromas and other tissues revealed four candidates for the modification of neurofibroma formation: CENTA2, RAB11FIP4, C17orf79, and UTP6.

Differential gene expression between human schwannoma and control Schwann cells.

The NF2 gene encodes the tumour suppressor protein merlin. The mutation of a single allele of this gene causes the autosomal dominantly inherited disease neurofibromatosis type 2 (NF2), which is characterized mainly by vestibular schwannoma carrying a second hit mutation. Complete lack of merlin is also found in spontaneous schwannomas and meningiomas. As the events leading to schwannoma development are largely unknown we investigated the differences in gene expression between schwannoma cells from NF2 patients and normal human primary Schwann cells by cDNA array analysis. We identified 41 genes whose expression levels differed by more than factor 2. Most of these clones were corroborated by real-time reverse transcription polymerase chain reaction analysis. By this method a total of seven genes with increased and seven genes with decreased mRNA levels in schwannoma compared with normal Schwann cells could be identified. Regulated clones, some of which not been described in Schwann cells earlier, included matrix metalloproteinase's, growth factors, growth factor receptors and tyrosine kinases.