Juvenile angiofibromas (JAs) are rare benign tumors arising almost exclusively in the posterior nasal cavity of adolescent males. While male sex predominance and tumor manifestation during adolescence are well known clinical features, their genetic causes are still unknown. Observation of an increased androgen binding rate to the cytosol of JAs and immunohistological finding of strong AR expression have suggested involvement of the androgen receptor (AR) in JA biology. In the present study, we investigated sex chromosome distribution and the expression of the AR gene in JAs of 7 males using two-color in situ hybridizations. Probes specific for the centromeres of chromosomes 1, X, and Y as well as a probe specific for the AR gene were used for investigation of paraffin-embedded JA tissue. Significant aberrations of the chromosome 1 were not observed. In 6 out of 7 analysed JAs derived from male patients we observed a significant loss of the chromosome Y in 11.5 to 63.8% (mean value: 31.3%). A gain of chromosome X was seen in 5 out of 7 JAs with the finding of two chromosomes X in 12 to 34% (mean value: 25%) of the analyzed nuclei. As each chromosome X revealed nearly almost one AR gene signal without evidence for amplifications, in 11.5 to 30% of the JA nuclei (mean value: 23.8%) two copies of the AR gene were observed. Our data indicate a significant loss of chromosome Y in combination with a gain of chromosome X in JAs. A gain of chromosome X leads to AR gene gain indicating that JAs are androgen-dependent tumors. This is supported by the finding that β-catenin known to be overexpressed in JAs acts as a co-activator of the AR.

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