دورية أكاديمية

P14.05.B Plasma-EV based liquid biopsy for precision medicine in the treatment of glioblastoma

التفاصيل البيبلوغرافية
العنوان: P14.05.B Plasma-EV based liquid biopsy for precision medicine in the treatment of glioblastoma
المؤلفون: Faletti, S, Zaccheroni, E, Osti, D, Del Bene, M, DiMeco, F, Pelicci, G
المصدر: Neuro-Oncology ; volume 24, issue Supplement_2, page ii83-ii83 ; ISSN 1522-8517 1523-5866
بيانات النشر: Oxford University Press (OUP)
سنة النشر: 2022
مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology
الوصف: Background Glioblastoma (GBM) is a devastating and protean brain tumor. Diagnosis and molecular characterization rely on magnetic resonance imaging and brain biopsy which are challenged by low specificity/sensitivity and surgical risks. This hampers the longitudinal monitoring of patients with GBM, whose molecular dynamism ideally requires to refine the therapeutic plan in different disease stages. Extracellular vesicles (EVs) shed by GBM act as a reservoir of circulating biomarkers and can be easily collected through a blood sample, placing the rational to exploit them as a platform for liquid biopsy in GBM. Material and Methods We isolated EVs from 2ml of pre-operative platelet-free plasma by Size Exclusion Chromatography (SEC). EVs are characterized by (i) immunoblot and Fluorescent-Activated Cell Sorter (FACS) for the presence of EV markers; (ii) TEM for morphology and size; (iii) Nanoparticle Tracking Analysis (NTA) for size and concentration; (iv) RNAseq and ddPCR for EV-associated nucleic acid profiling. Results SEC allowed to define EV-enriched fractions expressing the EV-markers CD9, CD81, Flotillin1, lacking the non-EV marker Calnexin and depleted of the majority of plasma contaminants. EV quantification by NTA confirmed their enrichment in the plasma from GBM patients. EV-RNA length (< 200nt) and total yield (1-10ng among different samples) allowed a successful RNAseq library preparation for downstream identification of splicing isoforms, translocations, fused mRNAs, and expression level of GBM-specific transcripts. The ddPCR-based analysis of mutations and copy number alterations proved the ability of cell-derived EV-DNA to recapitulate the alterations of the parental cells. Although the yield of plasma-EV-DNA is low (around 1ng), this paves the way to optimize the isolation/analysis of plasma EV-DNA to permit tumor profiling. Conclusion Plasma-EV based liquid biopsy could implement the personalisation of GBM care for every timepoint of the disease course. Increased plasma-EV ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1093/neuonc/noac174.290
الإتاحة: https://doi.org/10.1093/neuonc/noac174.290Test
https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_2/ii83/45691904/noac174.290.pdfTest
حقوق: https://academic.oup.com/pages/standard-publication-reuse-rightsTest
رقم الانضمام: edsbas.88F37499
قاعدة البيانات: BASE