Die Untersuchung zellfreier DNA durch Liquid Biopsy in der Medizin

Zusammenfassung

Bei Diagnostik und Monitoring von Tumoren stellten bisher bild- oder biopsiebasierte Verfahren den Goldstandard dar. Neuere Verfahren könnten dieses Vorgehen verändern. So ist es gelungen, zirkulierende Tumorzellen direkt aus dem peripheren Blut zu isolieren und zu charakterisieren. Intratumorale Zellheterogenitäten stellen sich hierbei jedoch als problematisch dar, da diese zu fehlerhaften Betrachtungen führen können. Durch die Analyse von zellfreier Tumor-DNA aus Tumorabbauprodukten im peripheren Blut (sog. Liquid Biopsy) mittels neuester Sequenziertechniken (NGS) können nun auch sehr komplexe Zusammenhänge analysiert werden. Dadurch werden sowohl Einzelgenveränderungen als auch gesamtgenomische Kopienzahlveränderungen (sog. copy number variations, CNV) erkennbar. Bei über 90% der malignen Tumoren lassen sich größere CNV-Abweichungen nachweisen. Der Grad der CNV-Abweichung vom Normalzustand lässt sich in copy number instability (CNI)-Scores standardisieren. Dadurch ist der CNI-Score ein vielversprechender klinischer Biomarker für die Risikostratifizierung und das individualisierte Therapiemonitoring mit dem Potenzial, die Gesundheitskosten und die Krankheitsbelastung für Krebspatienten zu senken.

Abstract

In diagnosis and monitoring of tumors, image- or biopsy-based methods have so far been the gold standard. However, newer methods could change this approach. It is now possible to isolate and characterize circulating tumor cells from peripheral blood directly. Intratumoral cell heterogeneities, however, are problematic because they can lead to incorrect observations. By analyzing cell-free tumor DNA from tumor degradation products in peripheral blood (Liquid Biopsy), even very complex relationships can now be analyzed by using the latest sequencing techniques (NGS). This allows both single gene changes and total genomic copy number changes, so-called copy number variations (CNV), to be identified. In more than 90% of malignant tumors, larger CNV deviations can be detected. The degree of CNV deviation from the normal state can be standardized by a copy number instability (CNI) score. This makes the CNI score a promising clinical biomarker for risk stratification and individualized therapy monitoring with the potential to reduce health costs and disease burden for cancer patients.

Schlüsselwörter

freie DNA - Liquid Biopsy - CNI-Score - Tumormarker - zirkulierende Tumorzellen - prediktiver Wert

Key words

freeDNA - liquid biopy - CNI score - biochemical tumor marker - circulating tumor cells - predictive value

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