Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma
Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it require...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 15, 2024
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| In: |
EMBO molecular medicine
Year: 2024, Volume: 16, Issue: 7, Pages: 1560-1578 |
| ISSN: | 1757-4684 |
| DOI: | 10.1038/s44321-024-00082-6 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44321-024-00082-6 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1038/s44321-024-00082-6 
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| Author Notes: | Mark Sementsov, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, Isabel Heidrich, Beate Volkmer, Rüdiger Greinert, Peter Mohr, Ronald Simon, Julia-Christina Stadler, Darryl Irwin, Claudia Koch, Antje Andreas, Benjamin Deitert, Verena Thewes, Andreas Trumpp, Andreas Schneeweiss, Yassine Belloum, Sven Peine, Harriett Wikman, Sabine Riethdorf, Stefan W Schneider, Christoffer Gebhardt, Klaus Pantel & Laura Keller |
MARC
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| 245 | 1 | 0 | |a Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma |c Mark Sementsov, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, Isabel Heidrich, Beate Volkmer, Rüdiger Greinert, Peter Mohr, Ronald Simon, Julia-Christina Stadler, Darryl Irwin, Claudia Koch, Antje Andreas, Benjamin Deitert, Verena Thewes, Andreas Trumpp, Andreas Schneeweiss, Yassine Belloum, Sven Peine, Harriett Wikman, Sabine Riethdorf, Stefan W Schneider, Christoffer Gebhardt, Klaus Pantel & Laura Keller |
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| 520 | |a Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis. | ||
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