Abstract B22: Capturing L1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers as a way to track tumor development
Notice bibliographique
Résumé
Abstract Endometrioid ovarian cancer (ENOC) and clear cell ovarian cancer (CCOC) share a common precursor lesion, endometriosis (ectopic growth of uterine lining), hence the designation endometriosis-associated ovarian cancer (EAOC). Women with endometriosis have up to three-fold increased risk of developing ENOC and CCOC. Efforts have been made to look for biomarkers that can help identifying women at risk of developing cancer; however, there are currently no biomarkers that stratify risk of cancer development. We performed whole-genome sequencing (WGS) on 29 ENOC and 35 CCOC cases and observed a frequent transduction event originating from an active LINE-1 (L1) retrotransposable element in the TTC28 gene. Such event occurred in 34% (10/29) of ENOC, and 31% (11/35) of CCOC cases. L1 retrotransposons are repetitive, mobile genetic elements capable of taking downstream DNA fragments and inserting them into random genomic locations via a process called 3’ transduction. Approximately 70-100 different potentially active L1s are epigenetically silenced in normal tissues, but tend to be reactivated in cancers. We subsequently used PCR to validate these TTC28-L1 transductions, and compared their presence to single nucleotide variations (SNVs) and frameshift mutations in formalin-fixed, paraffin-embedded (FFPE) tumor tissues from different tumor sites for 4 ENOC and 3 CCOC cases. We found that these transduction events along with classical driver mutations were almost ubiquitous across the tumor sites, suggesting these L1 events likely occurred early in the malignant transformation of EAOCs. We developed a low-input, probe-based capture assay to test the presence of TTC28-L1 transductions as an alternative method to performing WGS. Oligonucleotide probes tiling 1 kb downstream of active L1s are used to capture DNA fragments containing the transduced DNA, and the fragments are sequenced on the MiSeq next-generation sequencing platform. Analyses are performed using the Geneious software and the published bioinformatics tool Socrates, specific for detecting DNA fragments with split reads (fragments with ends aligning to different parts of the genome). We successfully validated the assay on 9 cases with WGS data: 7 EAOC cases with TTC28-L1 transductions and 2 EAOC cases without TTC28-L1 transductions. DNA extracted from frozen tumor and buffy coat (normal control) were used for each case, and FFPE tissues were used for selected cases. All reads containing the transduction events aligned to genomic coordinates corresponding to the WGS data. While L1-mediated DNA transductions are often passenger events during tumorigenesis, our data suggest that they likely occur early in ovarian cancer tumorigenesis. Our data show that this probe-based capture assay provides an alternative method to WGS, and may be useful in detecting active 3’ transductions in novel cases to track the development of ovarian tumors. Citation Format: Zhouchunyang Xia, Dawn Cochrane, Michael Anglesio, Winnie Yang, Miguel Alcaide, Tayyebeh Nazeran, Janine Senz, Amy Lum, Ali Bashashati, Yikan Wang, Ryan Morin, Sohrab Shah, David Huntsman. Capturing L1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers as a way to track tumor development. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B22.
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 | 0,003 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 ».