MDB-71. IDENTIFICATION AND DESCRIPTION OF A NOVEL TYPE OF MEDULLOBLASTOMA
Bibliographic record
Abstract
Abstract BACKGROUND Medulloblastoma (MB) is one of the most frequent high-grade brain tumor types of childhood and adolescence. Based on biology, histology, and its clinical course, MB is a heterogeneous disease with four different molecular types (WNT, SHH, Group 3, and Group 4), which are most reliably distinguishable by their global DNA methylation pattern. METHODS We analyzed DNA methylation (n=47), copy number variants, transcriptomic data (n=7) and histology (n=28) of a previously unrecognized type of MB. RESULTS As a result of integrating DNA methylation data of >2,600 MB and screening of >140,000 data sets uploaded to the DKFZ brain tumor classifier (www.molecularneuropathology.org), we identified a small group of MB that displayed a homogeneous DNA methylation pattern, which was clearly distinct from previously known MB types. Tumors within this group have also been recognized as a separate methylation class by latest versions of the classifier, which has provisionally been named medullomyoblastoma (MB_MYO). Transcriptomic data were similarly distinct from other MB types. Comparison of these data to various cell types of the developing hindbrain revealed transcriptional similarities to precursor cells of the rhombic lip with signatures of WNT signaling and myogenic differentiation. In line with the latter findings, 2/11 cases with DNA sequencing data harbored hotspot CTNNB1 mutations and 5/28 cases showed a myogenic differentiation based on histology. MYC amplifications were present in 11/47 cases, corresponding to a higher fraction of MYC-amplified tumors compared to all known MB types. Median age at diagnosis in this cohort was 16 years, and five-year overall survival was ~75 %. CONCLUSIONS In summary, we describe a novel type of MB identified by DNA methylation profiling that likely needs to be addressed separately during the retrospective analyses of MB patient cohorts, for the design of future clinical trials, and when evaluating targeted therapies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".