Subtype-specific expression and genetic alterations of the chemokinereceptor geneCXCR4 in medulloblastomas
Bibliographic record
Abstract
Recent findings indicate that the chemokine receptor Cxcr4 is essential for normal development of the cerebellar cortex. As medulloblastomas (MBs), the most common malignant brain tumors of childhood, are believed to arise from neuronal cerebellar precursors, we asked whether there is a potential role for Cxcr4 in the pathogenesis of MB. RT-PCR and immunohistochemistry revealed expression of Cxcr4 in different variants of MBs. Whereas 18/20 classic MBs showed very low levels of CXCR4 mRNA, high amounts were expressed in 17/18 desmoplastic and 6/7 extensively nodular MBs. In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75NTR or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer. Because Cxcr4 is important for migration and cell cycle control of granular precursors, we screened for mutations in the coding region by SSCP and gene sequencing. In a series of 90 MBs and 8 MB cell lines, we found one germline and one somatic mutation resulting in amino acid substitutions in the first (Ile53Leu) and second (Asp97Asn) transmembrane regions, respectively. These data suggest that Cxcr4 may be involved in the pathogenesis of MBs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 source (direct Gemma or distilled Codex), 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".