Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations?

Jennifer Klump, Ulrike Phillipp, Marie Follo, Anna Eremin, Hannes Lehmann, Sigrun Nestel, Nikolas von Bubnoff, Irina Nazarenko*

*Corresponding author for this work
25 Citations (Scopus)

Abstract

Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity. Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis. Our results show that EV contain significantly higher amounts of total DNA as compared to the fc fraction. However, about ten-fold higher copy numbers of the wild type and mutant BRAF and cKIT were detected in the fcDNA fraction supporting its diagnostic value and pointing to differences in fc and EV DNA content.

Original languageEnglish
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number3
Pages (from-to)875-882
Number of pages8
ISSN1549-9634
DOIs
Publication statusPublished - 04.2018

Funding

Financial support: The work was supported by BMBF IB-GUS/RUS 01DJ15026 and ERA-RusPlus/ID110 Exodiagnos/BMWi ZIM collaboration project KF2979902CR4 to IN. The authors acknowledge e-cost Actions COST-BM2012-MEHAD and COST-BM1401–Raman4Clinics.

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