Genomic landscape of pineoblastoma.
Bibliographic record
Abstract
2028 Background: Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Overall survival rates are estimated at 50-60%, with younger patients ( < 5 years old) faring much worse (15-40%) despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of PB, the clinical significance of such alterations and the biology of sporadic cases remains unknown. Methods: We collected tumor tissue from 75 cases of PB diagnosed at their local centres from across five continents. We undertook global DNA methylation profiling and performed multiple orthogonal consensus clustering analyses to elucidate PB subgroups. Chromosomal copy number alterations were determined using Conumee then GISTIC 2.0. Mutational analysis was conducted by whole exome and RNA sequencing. Clinical data was analyzed with correlative statistical methods and outcomes were measured by Kaplan-Meier survival estimates. Results: We discovered that PBs comprise four molecular sub-types, designated groups 1 to 4, with characteristic copy number alterations and mutational patterns. These molecular sub-groups exhibit distinct clinical features and survival outcomes. While PB groups 1-3 arose in older children (median ages 5.2-12.6 years), group 4 PB was restricted to much younger children (median age 1.4 years). Group 4 PB exhibited the highest incidence of metastases (53%) and had the worst 5-year event-free survival (EFS) and overall survival (OS) at 7.7% and 16.7%, respectively. In contrast, group 2 patients had a 5-year EFS and OS of 100%, while groups 1 and 3 had intermediate outcomes (5-year EFS 36.1% and 53.3%, 5-year OS 68.1% and 53.3%, respectively). Conclusions: PBs divide into four groups, each with a distinct genetic and clinical profile. These findings will have important implications for precise patient stratification and form the foundation for preclinical studies of biology-informed therapies.
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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 | 0.001 |
| 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) | 0.003 | 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".