| Autor: |
Yan T; Department of Orthopaedic Oncology, People's Hospital, Beijing University, Beijing, China., Angelini M, Alman BA, Andrulis IL, Wunder JS |
| Jazyk: |
angličtina |
| Zdroj: |
Clinical orthopaedics and related research [Clin Orthop Relat Res] 2008 Sep; Vol. 466 (9), pp. 2184-9. Date of Electronic Publication: 2008 Jun 10. |
| DOI: |
10.1007/s11999-008-0332-2 |
| Abstrakt: |
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] |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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