Abstract A40: Profile of DNA repair status in a recently established panel of patient-derived ovarian carcinoma xenografts
Notice bibliographique
Résumé
Abstract Background and Purpose: A xenobank of patient derived (PDX) ovarian tumor samples has recently been established and shown to recapitulate the biological, histological, molecular and pharmacological features of human epithelial ovarian cancer (EOC). This EOC-xenobank consists of tumors with different sensitivity to cisplatin (DDP) from very responsive, responsive to resistant tumors. As DNA repair pathway represents an important driver in tumor response to DDP, we analyzed the mRNA expression of 20 genes involved in Nucleotide Excision Repair (NER), in Fanconi Anemia (FA), in Homologous Recombination (HR), in Base Excision Repair (BER), in Mismatch Repair (MMR) and Translesion Repair (TLR) pathways and the methylation pattern of some of these genes. The correlation with the response to a platinum-based therapy was also investigated. Methods: The genes selected have a key role in the BER (OGG1 and PARP1); in the NER pathway (ERCC1, XPA, XPF, XPD and XPG); the FA pathway (BRCA1, FANCA, FANCC, FANCD2 and FANCF); in TLR (PolEta), in MMR (MLH1), in MMEJ (PolQ) and in the transcription of some genes (CDK12). The mRNA levels were evaluated by RT-PCR with ad hoc validated primers. The promoter methylation of BRCA1, XPA, ERCC1 and MLH1 was studied by pyrosequencing, while for XPG and FANCF no predesigned assays were available and we evaluated their methylation status following reported assays. Results: We demonstrated: i) all the DNA genes considered were variably expressed in all the 44 PDX analyzed, with no specific istotype-specific cluster of expression; ii) in high grade seros/endometriod PDXs, the CDK12 mRNA expression levels positively correlated with the expression of TP53BP1, PALB2, XPF and PolB; iii) high grade serous/endometriod PDXs with TP53 mutation had statistically significant higher levels of PolQ, FANC-D2, RAD51 and Pol beta than high grade TP53 wild type PDXs; iv) BRCA1 was found to be hypermethylated in 48% of the xenografts. However, no correlation between mRNA levels and methylation status of the considered CpG islands was found; v) only the mRNA levels of CDK12, PALB2 and XPF inversely correlated with the in vivo DDP antitumor activity. Conclusions: These data suggest the mRNA expression levels of targeted DNA repair pathway-related genes as PALB2, XPF and CDK12 predict the response to a platinum based therapy in ovarian cancer, even if they need to be prospectively validated in cohort of ovarian cancer patients. Citation Format: Federica Guffanti, Maddalena Fratelli, Monica Ganzinelli, Francesca Ricci, Maria Rosa Cappelletti, Damiele Generali, Francesca Bizzaro, Raffaella Giavazzi, Giovanna Damia. Profile of DNA repair status in a recently established panel of patient-derived ovarian carcinoma xenografts [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr A40.
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 | 0,001 |
| 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 | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 ».