Bibliographic record
Abstract
Mutations in Hedgehog (Hh) pathway genes such as Patched1 are of established importance in Basal cell carcinoma (BCC). However, BCC is unusual because it has indolent behaviour and rarely metastasises. Hh pathway gene mutations are rare in cancers with more typical malignant behaviour, leading to the hypothesis that the pathway plays an important role in BCC but has limited importance in cancers with typical malignant behaviour. This has been addressed in three ways. First, evidence that superficial BCC is a clonal proliferation driven by alterations at the Patched1 locus was sought. Second, evidence of Wnt pathway activation in BCC was sought by looking for nuclear accumulation of -catenin, because Wnt is a putative Hedgehog pathway target gene. Third, to determine whether the Hh pathway was important in a cancer with typical malignant behaviour, breast cancer was studied. In superficial BCC, microdissection of individual tumour nests and analysis for LOH in six cases using three microsatellite markers at the Patched1 locus was performed. Only one of the microsatellites was successfully employed. In four of the cases, all nests showed no LOH and in two cases, all nests lost the same allele. Concordant patterns of allelic loss/retention within cases represented strong evidence of clonality. In addition, the two cases with LOH suggested that clonal proliferation in superficial BCCs might be driven by Patched1 alternations. Accumulation of nuclear -catenin was found in 20 out of 86 BCCs and had a significant relationship with proliferation, indicating that the Hh pathway may act through its target genes. Alternative factors influencing -catenin distribution were sought: no relationship between nuclear -catenin and expression of E-cadherin was seen and no -catenin mutations in eight cases were found. Four breast cancer cell lines and HBL100, derived from normal mammary epithelium, showed substantially lower expression of Hh pathway target genes than BCC and were unresponsive to the pathway ligand, Sonic Hh, suggesting that the pathway is not important in this tumour. However, a relationship was found between the expression of Patched1 and in vitro invasion, the importance of which is uncertain. In conclusion, these results support the hypothesis that the Hh pathway is important in BCC but not in cancers with typical malignant behaviour.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".