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: | , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2023
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| 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 
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| 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 |
MARC
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| 100 | 1 | |a Van der Leest, Paul |e VerfasserIn |0 (DE-588)130659524X |0 (DE-627)186638936X |4 aut | |
| 245 | 1 | 0 | |a 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 |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a circulating tumor DNA | |
| 650 | 4 | |a liquid biopsy | |
| 650 | 4 | |a metastatic non-small cell lung cancer | |
| 650 | 4 | |a progressive disease | |
| 650 | 4 | |a resistance mutations | |
| 700 | 1 | |a Janning, Melanie |e VerfasserIn |0 (DE-588)1254060979 |0 (DE-627)1796679704 |4 aut | |
| 700 | 1 | |a Rifaela, Naomi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Azpurua, Maria L. Aguirre |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kropidlowski, Jolanthe |e VerfasserIn |4 aut | |
| 700 | 1 | |a Loges, Sonja |d 1973- |e VerfasserIn |0 (DE-588)129285463 |0 (DE-627)480392161 |0 (DE-576)297579002 |4 aut | |
| 700 | 1 | |a Lozano, Nicolas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sartori, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Irwin, Darryl |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lamy, Pierre-Jean |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hiltermann, T. Jeroen N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Groen, Harry J. M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pantel, Klaus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kempen, Léon C. van |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wikman, Harriet |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schuuring, Ed |e VerfasserIn |4 aut | |
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