MB-102HEMATOGENOUS DISSEMINATION OF MEDULLOBLASTOMA DRIVES LEPTOMENINGEAL DISEASE
Bibliographic record
Abstract
Metastasis to the leptomeningeal space is a determinat of poor prognosis in medulloblastoma. Current consensus describes that medulloblastoma cells are shed from the primary tumor into the CSF, survive through the spinal fluid to re-grow on the leptomeningeal surface of the pia and establish metastatic colonies. To understand the mechanism of metastasis of medulloblastoma we undertook whole genome sequencing on matched trios of primary tumor, metastases, and peripheral blood. We observed somatic mutations at low clonal frequency in the blood samples, consistent with circulating tumor cells. This finding suggested the hypothesis that leptomeningeal metastases arise through hematogenous, rather than a CSF route. We identified circulating tumor cells (CTC) in the blood of transgenic mice bearing metastatic medulloblastoma, and CTCs in mice intra-cranially implanted with patient derived MB xenografts. Surprisingly, when different human medulloblastoma cells are implanted in the flank of immunocompromised mice, the MB cells colonize the leptomeningeal space. As these MB xenografts are not in continuity with the cerebrospinal fluid, they must have arisen through hematogenous dissemination. Finally we established a parabiosis model where two immunocompromised mice are surgically joined, and a common blood circulation is established. After parabiosis, one mouse is intra-cranially implanted with MB xenografts, and the mice are subsequently separated when the xenografted twin becomes symptomatic. The surviving twins are observed, and develop leptomeningeal metastases. Our data add a new layer of complexity to the existing paradigm of CSF mediated dissemination of medulloblastoma by demonstrating the capacity of medulloblastoma to spread through the blood system.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".