Identification of CTNNB1 mutations, CTNNB1 amplifications, and an Axin2 splice variant in juvenile angiofibromas.

Juvenile angiofibromas (JAs) are benign fibro-vascular tumors occurring nearly exclusively in adolescent males. Even less is known about this rare tumor entity, alterations affecting the Wnt-pathway seem to play a pivotal role in tumor biology as activating CTNNB1 mutations have been detected. However, the knowledge of Wnt-pathway changes is still limited. Therefore, we aimed to determine in JAs further insight into Wnt/β-catenin pathway components. In our present study, genetic alterations of the Wnt-pathway members CTNNB1, APC, GSK3β, and Axin2 detected by metaphase comparative genomic hybridization (CGH) were shown to result in elevated transcript levels in the majority of JA samples compared to nasal mucosa stroma (p < 0.001, p = 0.001, p = 0.046, and p = 0.006, respectively). Additionally, amplifications of CTNNB1 were validated by fluorescence in situ hybridization (FISH) and genomic qPCR. Moreover, our mutation analysis detected already known mutations as well as, to the best of our knowledge, mutations and an interstitial deletion of CTNNB1 not described in JAs before. Additionally, a so far unknown transcribed Axin2 splice variant was found, but no further Axin2 mutations. Taken together, our current study supports the importance of aberrant Wnt-signaling as a common event in JAs, most likely by the observed genetic alterations driven by mutations, interstitial deletions but also amplifications of CTNNB1 contributing to the stabilization of β-catenin.