PATCHED-ONE or SMOOTHENED Gene Mutations Are Infrequent in Chondrosarcoma
Bibliographic record
Abstract
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]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".