EPND-07. MOLECULAR HETEROGENEITY AMONG PEDIATRIC POSTERIOR FOSSA EPENDYMOMA
Bibliographic record
Abstract
Previously, we have identified nine distinct molecular groups of ependymoma across all age groups, three in each major anatomical compartment of the CNS: spinal, posterior fossa, and supratentorial. These nine molecular groups are genetically, epigenetically, transcriptionally, demographically, and clinically distinct. Pediatric intracranial ependymomas are either affiliated with the RELA and YAP1 supratentorial groups or with the posterior fossa PFA group. RELA and YAP1 ependymomas harbor recurrent and distinct fusion genes that drive the disease, but PFA ependymomas lack significant recurrent mutations, and the specific oncogenic events underlying these tumors remain undefined. Observing distinct outcomes among children with PFA ependymomas, we tested the hypothesis that further molecular diversity with clinical utility, including possible novel genetic alterations, may exist among these tumors. Genome-wide DNA methylation profiles of 681 pediatric PFA ependymomas were analyzed by unsupervised consensus hierarchical clustering and t-distributed stochastic neighbor embedding (tsne), which identified not only three major distinct molecular subgroups of PFA ependymoma: PFA-1, PFA-2, and PFA-3, but additional small subgroups that segregate within PFA-1 and PFA-2. Subgroups were characterized by distinct clinical and genetic characteristics; most PFA-3 tumors harbored 1q gain and occurred in children significantly older than those with PFA-1 and PFA-2 tumors. Some of the small subgroups demonstrated distinctive copy number alterations or gene mutations, e.g. H3 K27M. Outcome data revealed considerable heterogeneity among the different subgroups, overall survival at 5 years was >90% for one subgroup, but <20% for two others. We conclude that further molecular refinement of pediatric PFA ependymomas has clinical utility and the potential for enhanced risk assessment or therapeutic stratification. In addition, identification of PFA subgroups and further molecular heterogeneity within these subgroups may help to identify the drivers of PFA ependymomas.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".