Analysis of cell free DNA to predict outcome to bevacizumab therapy in colorectal cancer patients
To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 May 2024
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| In: |
npj Genomic Medicine
Year: 2024, Jahrgang: 9, Heft: 1, Pages: 1-10 |
| ISSN: | 2056-7944 |
| DOI: | 10.1038/s41525-024-00415-x |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41525-024-00415-x Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41525-024-00415-x 
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| Verfasserangaben: | Tom Venken, Ian S. Miller, Ingrid Arijs, Valentina Thomas, Ana Barat, Johannes Betge, Tianzuo Zhan, Timo Gaiser, Matthias P. Ebert, Alice C. O’Farrell, Jochen Prehn, Rut Klinger, Darran P. O’Connor, Brian Moulton, Verena Murphy, Garazi Serna, Paolo G. Nuciforo, Ray McDermott, Brian Bird, Gregory Leonard, Liam Grogan, Anne Horgan, Nadine Schulte, Markus Moehler, Diether Lambrechts, Annette T. Byrne |
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| 245 | 1 | 0 | |a Analysis of cell free DNA to predict outcome to bevacizumab therapy in colorectal cancer patients |c Tom Venken, Ian S. Miller, Ingrid Arijs, Valentina Thomas, Ana Barat, Johannes Betge, Tianzuo Zhan, Timo Gaiser, Matthias P. Ebert, Alice C. O’Farrell, Jochen Prehn, Rut Klinger, Darran P. O’Connor, Brian Moulton, Verena Murphy, Garazi Serna, Paolo G. Nuciforo, Ray McDermott, Brian Bird, Gregory Leonard, Liam Grogan, Anne Horgan, Nadine Schulte, Markus Moehler, Diether Lambrechts, Annette T. Byrne |
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| 520 | |a To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed on matched tumor and plasma samples, collected from 74 mCRC patients from the AC-ANGIOPREDICT Phase II trial (NCT01822444), and analysed for CIN and NFs. A validation cohort of plasma samples from the University Medical Center Mannheim (UMM) was similarly profiled. 61 AC-ANGIOPREDICT plasma samples collected before and following BVZ treatment were selected for targeted methylation sequencing. Using cfDNA CIN profiles, AC-ANGIOPREDICT samples were subtyped with 92.3% accuracy into low and high CIN clusters, with good concordance observed between matched plasma and tumor. Improved survival was observed in CIN-high patients. Plasma-based CIN clustering was validated in the UMM cohort. Methylation profiling identified differences in CIN-low vs. CIN high (AUC = 0.87). Moreover, significant methylation score decreases following BVZ was associated with improved outcome (p = 0.013). Analysis of CIN, NFs and methylation profiles from cfDNA in plasma samples facilitates stratification into CIN clusters which inform patient response to treatment. | ||
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