Abstract B18: MEG3 and MEG8 aberrant methylation associated with worst prognosis in an infant with neuroblastoma
Notice bibliographique
Résumé
Abstract Background: Neuroblastoma (NB) is an extremely rare pediatric cancer accounting for about 12% of childhood cancer-related deaths, due to its dismal prognosis in patients diagnosed over 18 months of age with disseminated disease. However, neonates and infants with neuroblastoma are expected to have a better evolution despite their stage and even unfavorable molecular characteristics. Here, we report an unusual case of low-risk neuroblastoma (stage 2B, nonamplified MYCN) in a 9-month-old girl with unfavorable outcome despite favorable prognostic factors. Material and Methods: We investigated the coding genes expression (mRNA) and long noncoding RNAs (lncRNAs) in primary and relapse tumors of this patient to look for genomic and epigenetic alterations that could explain the clinical evolution. The cytogenetic profiles of the primary and relapse tumor samples were also obtained. Three primary tumors from patients with neuroblastoma, all classified as stage 1 (INSS) and low-risk (below 18 months of age at diagnosis, nonamplified-MYCN, all alive and free of disease 60 months after diagnosis) were used as controls in RNA sequencing (RNA-Seq. Illumina®) and DNA methylation arrays (Illumina Infinium HumanMethylation450 BeadChip). Somatic copy number alterations were investigated in the primary and relapsed sample using the array-CGH methodology in a 180K platform (Agilent). Results: The cytogenetic profiles of both samples were quite identical, with few copy number alterations. No numerical chromosomal alterations (aneuploidies) were detected; both tumors carry segmental copy number alterations in common, most of them probably present in a nonmosaic state. The differential gene expression analysis based on fold-change (≤ -2 and ≥ 2), p < 0.005, and FDR < 0.05 was used in RNA-seq to identified gene differential expression in primary and relapsed tumors. Interestingly, only two lncRNA, the imprinted maternally expressed genes MEG3 and MEG8, were downregulated in both primary and relapse tumors. MEG3 targets p53 by either directly interacting with p53 or indirectly suppressing the negative regulator MDM2. In the case of MEG8, their functions in cancer remain unknown. Our study then focused on MEG3 and MEG8 methylation analysis. DNA methylation status of the study groups (primary, relapse tumors, and controls) strongly suggested that DMR that covers promoters was responsible for silencing MEG3 and MEG8 genes in primary and relapse tumors, resulting in downregulation of MEG3 and MEG8. Tumor samples from the patient were also used to perform methylation-specific MLPA (MSMLPA) (SALSA® probemix, MRC-Holland). Hypermethylated probes at MEG3 were identified in primary and relapse tumors when compared with controls. Conclusion: Furthermore, we hypothesized that the methylation gain of the MEG3 and MEG8 locus may be accentuated during cancer progression and therefore, the increased degree of MEG3 and MEG8 suppression was associated with the overall aggressiveness of neuroblastoma. Citation Format: Estela M. Novak, Thamiris Magalhaes Gimenez, Nathalia Halley Neves, Carolina Sgarioni Camargo Vince, Ana Cristina Victorino Krepischi, Rainer Marco Lopez Lapa, Lilian M. Cristofani, Israel Bendit, Vicente Odone Filho. MEG3 and MEG8 aberrant methylation associated with worst prognosis in an infant with neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B18.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 source (Gemma direct ou Codex distillé), 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 ».