Erschienen in:
01.09.2008 | Symposium: Molecular Genetics in Sarcoma
PATCHED-ONE or SMOOTHENED Gene Mutations Are Infrequent in Chondrosarcoma
verfasst von:
Taiqiang Yan, MD, Mark Angelini, MD, FRCSC, Benjamin A. Alman, MD, FRCSC, Irene L. Andrulis, PhD, Jay S. Wunder, MD, MSc, FRCS(C)
Erschienen in:
Clinical Orthopaedics and Related Research®
|
Ausgabe 9/2008
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Excerpt
Constitutive hedgehog signaling has been implicated in the tumorigenesis of cartilaginous neoplasia; however, a common mutational mechanism remains unknown. Some tumors exhibiting hedgehog pathway activation such as basal cell cancer frequently harbor PATCHED-ONE (PTCH-1) or SMOOTHENED (SMO) gene mutations. We therefore asked whether mutations of the hedgehog receptor genes PTCH-1 or SMO occur in cartilage tumors. Single-strand conformation polymorphism (SSCP) analysis with subsequent manual sequencing was performed to detect alterations of PTCH-1 and SMO in 46 cartilage tumors. SSCP detected five shifts in the PTCH-1 gene and two shifts in SMO. Direct DNA sequencing revealed the five shifts in PTCH-1 were caused by silent nucleotide alterations. The two SMO shifts were the result of the same missense mutation (783G>A) and occurred in one dedifferentiated chondrosarcoma and a synovial chondromatosis. The patient with chondromatosis also carried this same mutation in the germline. However, this mutation was also identified in leukocyte DNA from three of 127 (2.4%) control subjects without cartilage tumors, suggesting it may represent a rare SMO variant. Constitutive activation of the hedgehog signaling pathway in chondrosarcoma is rarely caused by PTCH-1 or SMO mutations. …