Abstract LB-130: Abnormal expression of SWI/SNF chromatin remodeling complex genes in lung cancer
Notice bibliographique
Résumé
Abstract Objective: To study deregulation of the SWI/SNF chromatin remodeling complex in lung cancer tumors and cell lines with the emphasis on SMARCA2, SMARCA4 and ARID1A. Background: The DNA in each mammalian cell is compacted about 5000 fold into chromatin, and in the compacted state is unavailable for transcription. This compaction is controlled by three mechanisms: including the ATP-dependent chromatin remodeling complex SWI/SNF, consisting of 20 genes that code for about 12 protein subunits (some of which can substitute for each other). There are over 280 possible subunit permutations, influencing transcription, chromatin binding and remodeling, and tissue and gene specificity. Several subunit genes function as tumor suppressor genes (TSGs) including the interchangeable ATP catalytic components SMARCA2 (protein = BRM) and SMARCA4 (protein = BRG1) and the ARID1A (protein = BAF250a) accessory gene. The catalytic components are known to be inactivated in several cancers including lung, and ARID1A in ovarian cancer. Materials and Methods: Up to 58 cell lines and 60 non small cell lung cancer tumors arising in smokers and never smokers were studied. NextGen and Sanger sequencing of the SWI/SNF complex genes were performed on the cell lines. Western blots of nuclear extracts, methylation and qPCR were also performed on cell lines. Genome wide gene copy number (by SNP analyses) and microarray expression studies were performed on the tumors and cell lines. Immunostaining (for BRG1 and BAF250a) were performed on lung cancer microarrays. Results: Mutations rates in NSCLC lines were: SMARCA4 28% (mainly homozygous deletions), SMARCA2 0%, ARID1A 11% (mainly heterozygous point mutations). However, a marked decrease in nuclear protein expression was frequently present in NSCLC lines: BRG1 28%, BRM 28%, BAF250a 31%. Loss of BRG1, BRM, or BAF250a was present in 41% of the NSCLC lines, and 16% had loss of two or three. Combined analyses with microarray expression, immunostaining and qPCR studies of these three genes indicated frequent low expression in both NSCLC tumors and cell lines. In addition, DNA copy number by SNP analyses of NSCLC tumors indicated widespread loss of alleles of multiple members of the SWI/SNF complex. Evidence for epigenetic inactivation of one or more complex genes was present. Conclusions: Our data indicate frequent inactivation of one or more members of the SWI/SNF complex by a variety of mechanisms including deletions, mutations, epigenetic, transcriptional and translational control. The predicted downstream effects on transcription and histone regulation are likely to be widespread and possibly demonstrating cell type and gene specific effects. Although highly complicated, elucidation of the precise chromatin complex abnormalities, mechanisms and downstream effects indicate the possibility of multiple new therapeutic targets for lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-130. doi:10.1158/1538-7445.AM2011-LB-130
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 | 0,001 | 0,000 |
| 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 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 ».