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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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Main Authors: Van der Leest, Paul (Author) , Janning, Melanie (Author) , Rifaela, Naomi (Author) , Azpurua, Maria L. Aguirre (Author) , Kropidlowski, Jolanthe (Author) , Loges, Sonja (Author) , Lozano, Nicolas (Author) , Sartori, Alexander (Author) , Irwin, Darryl (Author) , Lamy, Pierre-Jean (Author) , Hiltermann, T. Jeroen N. (Author) , Groen, Harry J. M. (Author) , Pantel, Klaus (Author) , Kempen, Léon C. van (Author) , Wikman, Harriet (Author) , Schuuring, Ed (Author)
Format: Article (Journal)
Language:English
Published: 2023
In: International journal of molecular sciences
Year: 2023, Volume: 24, Issue: 17, Pages: 1-14
ISSN:1422-0067
DOI:10.3390/ijms241713390
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms241713390
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/17/13390
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Author Notes: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
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Summary: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.
Item Description:Veröffentlicht: 29. August 2023
Gesehen am 19.10.2023
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms241713390

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