Abstract P1-05-27: Evaluation of the Oncomine focus and comprehensive assays for therapeutic stratification in early hormone receptor positive breast cancers
Notice bibliographique
Résumé
Abstract Large-scale sequencing initiatives have revealed a wealth of common and novel variants as well as copy-number aberrations, across different solid tumours and hematological malignancies. The growing list of variants/aberrations can sometimes be matched to specific therapeutics. Such “actionable mutations/changes” hold promise for personalized treatment, as treatments could be tailored to molecular abnormalities, rather than disease site. In breast cancer, women with hormone positive early breast cancer continue to experience improved survival on adjuvant anti-hormone therapy, but even today, a significant number of women continue to progress. Therefore there is not only a need to identify those women for whom current therapies are insufficient, but to identify alternative therapeutic interventions. The ThermoFisher Scientific Oncomine™ Focus and Oncomine™ Comprehensive Assays (OFA and OCA) are based on the Ion Torrent™ next-generation sequencing platform and Ion AmpliSeq™ library preparation technology, coupled to the Oncomine™ Knowledgebase, for target selection, variant calling, and data annotations. Both panels interrogate the most referenced oncology biomarker variants that are matched to curated published evidence from clinical trials supporting the matching of driver genetic variants with relevant potential clinical therapeutic options. The ability to identify SNVs, CNVs and fusion events in a single assay provides an unprecedented approach to maximizing the molecular information to be derived from a single tumour sample. To explore the value of the Oncomine™ assays in early invasive breast cancers, we have performed a pilot study to assess the reproducibility and accuracy of the OFA and OCA from nucleic acids extracted from formalin-fixed paraffin embedded tissues. In addition to the sequencing and copy-number data generated by these assays, we will compare these results to copy-number information generated using the Oncoscan® (Affymetrix)copy-number assay as well as information derived by Multiplex Ligation-dependent Probe Amplification-based panels (MRC-Holland) and Fluorescent in situ Hybridization (FISH). Our preliminary analyses of 35 invasive breast cancers by Oncoscan® identified the frequent whole chromosomal gains of 2, 3, 5, 7, 18, 19 and 20; gains of 1q, 7p, 8q, 11p, 16p, 17q; losses at 1p, 8p, 11q, 13, 16q, 17p and chromosome 18. High level amplifications were also identified for breast cancer related genes such as ERBB2, CCND1, MYC, FGFR1; in addition to the frequent losses of TP53, RB1, CDKN2A. Copy-number changes were confirmed by locus-specific FISH and MLPA. Data generated from the OFA and OCA from these same samples will be compared to the other platform findings and provide a snapshot of the mutational landscape of early breast cancers across these pan-cancer panels. Having established the robustness and accuracy of the assays, the applicability of the OCA in the context of improved stratification for breast cancers for prognostic and predictive tests will be discussed. Citation Format: Bayani J, Crozier C, Zhang NX, Amemiya Y, Quintayo MA, Yan FJ, Dion D, Mccormack S, Yaffe M, Seth A, Feilotter H, Bartlett JMS. Evaluation of the Oncomine focus and comprehensive assays for therapeutic stratification in early hormone receptor positive breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-27.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 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 ».