The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4.

Subungual exostosis is a benign bone- and cartilage-forming tumor known to harbor a pathognomonic t(X;6)(q22;q13-14). Using global gene expression analysis and quantitative real-time PCR, we could show that this translocation results in increased expression of the IRS4 gene, presumably due to disruption and/or exchange of regulatory sequences with the translocation partner, the COL12A1 gene. A corresponding deregulation at the protein level could be demonstrated in primary cell cultures using a combination of fluorescence in situ hybridization and immunostaining. As the t(X;6) usually is the sole cytogenetic aberration in subungual exostosis, the deregulated expression of IRS4 is likely to be pathogenetically essential. The exact role of IRS4 is still poorly investigated, but IRS proteins are known to act as mediators of signaling from receptors, such as the insulin and insulin-like growth factor 1 receptors, and thus have an important effect on cell growth and survival.