TY - JOUR
T1 - The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4
AU - Mertens, Fredrik
AU - Möller, Emely
AU - Mandahl, Nils
AU - Picci, Piero
AU - Perez-Atayde, Antonio R.
AU - Samson, Ignace
AU - Sciot, Raf
AU - Debiec-Rychter, Maria
PY - 2011/1/15
Y1 - 2011/1/15
N2 - 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.
AB - 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.
KW - COL12A1
KW - collagen
KW - insulin receptor substrate
KW - IRS4
KW - subungual exostosis
KW - translocation
UR - http://www.scopus.com/inward/record.url?scp=78649562755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649562755&partnerID=8YFLogxK
U2 - 10.1002/ijc.25353
DO - 10.1002/ijc.25353
M3 - Article
C2 - 20340132
AN - SCOPUS:78649562755
VL - 128
SP - 487
EP - 491
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -