Abstract 3093: Unravelling the biology of aggressive and therapy-resistant embryonal tumors with multilayered rosettes (ETMR)
Bibliographic record
Abstract
Abstract Embryonal tumor with multilayered rosettes (ETMR) is a highly aggressive embryonal CNS tumor, which predominantly affects children under the age of three to four years and is associated with a highly aggressive disease course with reported overall survival times ranging from 5-30 months. As these tumors have often been misdiagnosed as medulloblastoma or CNS-PNETs it was thought that ETMR is a very rare tumor. However, now molecular tools are available to detect ETMR and distinguish them from other brain tumors it has become clear that it is one of the most common brain tumors among infants. Amplification of a miRNA cluster at 19q13.42 and high expression of LIN28A have been identified as molecular hallmarks of ETMR, affecting 95-100% of samples tested and are considered unifying molecular diagnostic markers to detect them and distinguish from other brain tumors. Three histological variants of ETMR are known. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). A comprehensive clinical, pathological, and molecular analysis of 97 cases of these fatal brain neoplasms identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. In particular, DNA methylation (Illumina 450k arrays) and gene expression data (Affymetrix 133plus2.0 arrays) showed that the three histological variants of ETMR are biologically indistinguishable but together highly distinct from other pediatric brain tumors. In order to better understand the biology of these highly aggressive pediatric CNS malignancies, we performed whole genome DNA sequencing of 15 tumor-normal pairs including 3 recurrences, complemented by (mi)RNA sequencing of tumor RNA. Mutations detected included mutations in TP53, CTNNB1, and mutations affecting the miRNA processing pathway. Chromothripsis was detected in several cases and in all cases affecting chromosome 19q. Finally, as DNA sequencing identified only very few somatic mutations per tumor, we next studied the epigenome of these tumors by performing whole genome bisulfite sequencing. Integrating these high throughput genomic analyses may now lead to alternative treatment strategies for these highly aggressive and therapy-resistant tumors. Citation Format: Marcel Kool, Natalie Jäger, Dominik Sturm, David T.W. Jones, Volker Hoverstadt, Ivo Buchhalter, Pascal Johann, Christin Schmidt, Marina Ryzhova, Paul A. Northcott, Pablo Landgraf, Marc Remke, Michael D. Taylor, Martin Hasselblatt, Ulrich Schüller, Annie Huang, Marie-Laure Yaspo, Andreas von Deimling, Roland Eils, Peter Lichter, Andrey Korshunov, Stefan M. Pfister. Unravelling the biology of aggressive and therapy-resistant embryonal tumors with multilayered rosettes (ETMR). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3093. doi:10.1158/1538-7445.AM2014-3093
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".