Patched-one or smoothened gene mutations are infrequent in chondrosarcoma.

Journal Article (Journal Article)

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. Singlestrand 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. [corrected]

Full Text

Duke Authors

Cited Authors

  • Yan, T; Angelini, M; Alman, BA; Andrulis, IL; Wunder, JS

Published Date

  • September 2008

Published In

Volume / Issue

  • 466 / 9

Start / End Page

  • 2184 - 2189

PubMed ID

  • 18543049

Pubmed Central ID

  • PMC2492993

Electronic International Standard Serial Number (EISSN)

  • 1528-1132

Digital Object Identifier (DOI)

  • 10.1007/s11999-008-0332-2


  • eng

Conference Location

  • United States