Epigenetic Silencing of the<i>HIC-1</i>Gene in Human Medulloblastomas
Bibliographic record
Abstract
The HIC-1 (hypermethylated in cancer) candidate tumor suppressor gene is located on chromosome 17p13.3, a region frequently deleted in medulloblastomas (MBs). MBs arising in the cerebellum represent the most common malignant brain tumors in children. In this study we have analyzed the sequence, methylation, and expression status of the HIC-1 gene in MBs. Hypermethylation of the 5'UTR and/or second exon of HIC-1 was detected in 33/39 (85%) of MB biopsies and in 7/8 (88%) of MB cell lines by methylation-specific PCR. There was a significant correlation (p < 0.001) between HIC-1 methylation and lack of transcription as determined by competitive RT-PCR. Treatment of the MB cell lines Daoy and MEB-MED-8A with 5-aza-2'deoxycytidine led to re-expression of HIC-1 transcripts, indicating a silencing of HIC-1 by CpG island methylation. Mutation analysis of the coding region of HIC-1 revealed a single deletion leading to an in-frame deletion of 4 amino acids in the second exon of HIC-1 (1/68, 1.5%). Our data indicate that a significant number of MBs exhibit strikingly reduced HIC-1 expression caused by altered CpG island methylation. These data suggest that epigenetic silencing of HIC-1 may well contribute to the pathogenesis in the majority of MBs.
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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 | 0.001 | 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) | 0.000 | 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".