Abstracts from the Thirteenth International Symposium on Pediatric Neuro-Oncology
Notice bibliographique
Résumé
Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive malignant CNS tumors of early childhood. Prognosis is extremely poor with median survival times ranging from 6 to 17 months. It has been recognized since the late 1990s that both AT/RTs and malignant rhabdoid tumors of the kidneys and other soft tissues are characterized by a loss of INI1 (aka SMARCB1, BAF47, hSNF5), a component of the SWI/SNF protein complex that regulates transcriptional activity through chromatin remodeling. In fact, loss of INI1 protein, as determined through immunohistochemistry, has become the de facto standard for diagnosis of AT/RTs. Any pediatric brain tumor showing loss of INI1 will generally be diagnosed as an AT/RT, regardless of histological characteristics. However, loss of INI1 has been found in other tumor types, including schwannomas and epithelioid sarcomas. Also, INI1 is not absent in approximately 15% of pediatric brain tumors that show diagnostic histological features for AT/RTs. Thus, INI1 may not be wholly specific to malignant rhabdoid tumors or AT/RTs. To identify potential diagnostic markers specific to AT/RT, 110 pediatric and adult brain tumor samples and 66 normal brain samples were analyzed for gene expression using Affymetrix U133Plus2 GeneChip microarrays. These arrays measure the expression of .54,000 probe sets, including all known human genes. The tumor samples analyzed included eight AT/RTs, as well as glioblastoma, medulloblastoma, large-cell medulloblastoma, ependymoma, pilocytic astrocytoma, rhabdomyosarcoma, meningioma, and radiation-induced tumors. AT/RT expression was compared individually to each other tumor type as well as to normal samples; p-values were adjusted using a false discovery rate of 0.05 which took into account all tests both within and across all groups. Fifty-nine unique genes were found to be overexpressed in the AT/RT samples when compared to all other groups (including normal); five genes were underexpressed. While generally INI1 was expressed at lower levels in AT/RTs than in all other samples, this did not achieve statistical significance for two groups (normal and meningioma). This result is not surprising, because microarrays measure mRNA levels rather than protein levels. Of the 59 genes statistically overexpressed in AT/RTs, 58 showed overlap in their range of expression with other tumor types. However, one gene was found that was consistently expressed in AT/RTs but showed almost no overlap in its range of expression compared to the tumor or normal samples: claudin 6 (CLDN6), a key component of tight junctions. There was an average difference of .50-fold between CLDN6 levels in AT/RTs versus all other tumors and similarly versus normal samples. Compared to medulloblastomas, the most difficult tumor type to discriminate from AT/RTs, CLDN6 was expressed .53-fold higher in AT/RTs with no overlap at all in expression levels. Analysis of protein abundance using Western blotting confirmed the microarray results. Thus the combination of INI1 as a negative marker and CLDN6 as a positive marker may be useful in defining AT/RTs for diagnostic purposes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».