Abstract 4355: The C19MC miRNA polycistron are frequent targets of gene amplification in aggressive primitive neuroectodermal brain tumors and encode oncogenic miRNAs that inhibit normal neural stem cell differentiation
Bibliographic record
Abstract
Abstract Embryonal brain tumors which include medulloblastoma and primitive neuroectodermal brain tumors (CNS-PNET) comprise the largest group of malignant pediatric brain tumors and account for substantial cancer related morbidity and mortality in childhood. Unlike medulloblastoma, a common, cerebellar PNET, few CNS-PNET arising in extracerebellar locations have been characterized. Lack of insight into the molecular pathogenesis of CNS-PNET is a major obstacle towards development of much-needed disease-specific models and treatments for these devastating tumors. In this study, we performed high-resolution DNA copy number analysis on a substantial collection of primary CNS-PNET obtained through an international collaborative group, and discovered a frequent amplicon in 25% (11/46) of CNS-PNET which span 34 protein coding genes and two miRNA clusters, C19MC and miR-371-373, on chr19q13.41. Detailed mapping studies revealed C19MC, which encode 54 primate-specific miRNAs, as the specific target of gene amplification resulting in striking tumor-specific overexpression of a sub-set of miRNAs, including miR-520 g and miR- 517c. Stable expression of miR-520 g and miR-517c promoted in vitro and in vivo oncogenicity and conferred cell survival in tumor cell lines. Strikingly expression of both miR-520g and 517c promoted growth and inhibited differentiation of untransformed normal human neural stem cells. Notably, clinicopathologic analyses revealed that C19MC amplification identifies a distinct group of CNS-PNET with similar gene expression profiles, characteristic histology, and much poorer survival. Our aggregate findings which point to C19MC as an important, new oncogenic locus in a human cancer, have significant implications for the diagnosis and clinical management of embryonal brain tumors in children. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4355.
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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 | 0.001 |
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".