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Detection and monitoring of tumor-derived mutations in circulating tumor DNA using the UltraSEEK lung panel on the MassARRAY system in metastatic non-small cell lung cancer patients

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA...

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Hauptverfasser: Van der Leest, Paul (VerfasserIn) , Janning, Melanie (VerfasserIn) , Rifaela, Naomi (VerfasserIn) , Azpurua, Maria L. Aguirre (VerfasserIn) , Kropidlowski, Jolanthe (VerfasserIn) , Loges, Sonja (VerfasserIn) , Lozano, Nicolas (VerfasserIn) , Sartori, Alexander (VerfasserIn) , Irwin, Darryl (VerfasserIn) , Lamy, Pierre-Jean (VerfasserIn) , Hiltermann, T. Jeroen N. (VerfasserIn) , Groen, Harry J. M. (VerfasserIn) , Pantel, Klaus (VerfasserIn) , Kempen, Léon C. van (VerfasserIn) , Wikman, Harriet (VerfasserIn) , Schuuring, Ed (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2023
In: International journal of molecular sciences
Year: 2023, Jahrgang: 24, Heft: 17, Pages: 1-14
ISSN:1422-0067
DOI:10.3390/ijms241713390
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms241713390
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/17/13390
Volltext
Verfasserangaben:Paul van der Leest, Melanie Janning, Naomi Rifaela, Maria L. Aguirre Azpurua, Jolanthe Kropidlowski, Sonja Loges, Nicolas Lozano, Alexander Sartori, Darryl Irwin, Pierre-Jean Lamy, T. Jeroen N. Hiltermann, Harry J. M. Groen, Klaus Pantel, Léon C. van Kempen, Harriet Wikman and Ed Schuuring
Beschreibung
Zusammenfassung:Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK® Lung Panel on the MassARRAY® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK®. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK® correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response.
Beschreibung:Veröffentlicht: 29. August 2023
Gesehen am 19.10.2023
Beschreibung:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms241713390

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