Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression
Background: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323002553 |
| _version_ | 1797324318529552384 |
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| author | Marzia Del Re Giovanna Irene Luculli Iacopo Petrini Andrea Sbrana Vieri Scotti Diego de Miguel Perez Lorenzo Livi Stefania Crucitta Mauro Iannopollo Francesca Mazzoni Martina Ruglioni Carmelo Tibaldi Emanuela Olmetto Irene Stasi Editta Baldini Giacomo Allegrini Lorenzo Antonuzzo Franco Morelli Andrea Pierini Nicola Panzeri Stefano Fogli Antonio Chella Christian Rolfo Romano Danesi |
| author_facet | Marzia Del Re Giovanna Irene Luculli Iacopo Petrini Andrea Sbrana Vieri Scotti Diego de Miguel Perez Lorenzo Livi Stefania Crucitta Mauro Iannopollo Francesca Mazzoni Martina Ruglioni Carmelo Tibaldi Emanuela Olmetto Irene Stasi Editta Baldini Giacomo Allegrini Lorenzo Antonuzzo Franco Morelli Andrea Pierini Nicola Panzeri Stefano Fogli Antonio Chella Christian Rolfo Romano Danesi |
| author_sort | Marzia Del Re |
| collection | DOAJ |
| description | Background: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score. Results: A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions. Conclusions: The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA. |
| first_indexed | 2024-03-08T05:54:20Z |
| format | Article |
| id | doaj.art-262397be030b4702b3e34b61b234daba |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-08T05:54:20Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-262397be030b4702b3e34b61b234daba2024-02-05T04:31:37ZengElsevierTranslational Oncology1936-52332024-03-0141101869Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progressionMarzia Del Re0Giovanna Irene Luculli1Iacopo Petrini2Andrea Sbrana3Vieri Scotti4Diego de Miguel Perez5Lorenzo Livi6Stefania Crucitta7Mauro Iannopollo8Francesca Mazzoni9Martina Ruglioni10Carmelo Tibaldi11Emanuela Olmetto12Irene Stasi13Editta Baldini14Giacomo Allegrini15Lorenzo Antonuzzo16Franco Morelli17Andrea Pierini18Nicola Panzeri19Stefano Fogli20Antonio Chella21Christian Rolfo22Romano Danesi23Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Thoracic Oncology Center, Tisch Cancer Center, Mount Sinai Hospital System & Icahn School of Medicine, Mount Sinai, New York, NY, USAUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyRadiation Oncology Unit, Oncology Department, AOU Careggi Firenze, Firenze, ItalyThoracic Oncology Center, Tisch Cancer Center, Mount Sinai Hospital System & Icahn School of Medicine, Mount Sinai, New York, NY, USADepartment of Experimental and Clinical Biomedical Sciences ''M. Serio'', University of Florence, Florence, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyOncology Department, Oncology Unit, San Jacopo Hospital, Pistoia, ItalyMedical Oncology, Careggi University Hospital, Florence, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Oncology, S. Luca Hospital, Lucca, ItalyRadiation Oncology Unit, Oncology Department, AOU Careggi Firenze, Firenze, ItalyDepartment of Oncology, Azienda USL Toscana Nord Ovest, Pisa, ItalyDepartment of Oncology, S. Luca Hospital, Lucca, ItalyDepartment of Oncology, Azienda USL Toscana Nord Ovest, Pisa, ItalyMedical Oncology, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, ItalyMedical Oncology Unit, Gemelli Hospital Molise, Campobasso, ItalyIntegrated Access, Roche, Monza, ItalyIntegrated Access, Roche, Monza, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyThoracic Oncology Center, Tisch Cancer Center, Mount Sinai Hospital System & Icahn School of Medicine, Mount Sinai, New York, NY, USACorresponding author.; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Unit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, Italy; Radiation Oncology Unit, Oncology Department, AOU Careggi Firenze, Firenze, Italy; Thoracic Oncology Center, Tisch Cancer Center, Mount Sinai Hospital System & Icahn School of Medicine, Mount Sinai, New York, NY, USA; Department of Experimental and Clinical Biomedical Sciences ''M. Serio'', University of Florence, Florence, Italy; Oncology Department, Oncology Unit, San Jacopo Hospital, Pistoia, Italy; Medical Oncology, Careggi University Hospital, Florence, Italy; Department of Oncology, S. Luca Hospital, Lucca, Italy; Department of Oncology, Azienda USL Toscana Nord Ovest, Pisa, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Medical Oncology Unit, Gemelli Hospital Molise, Campobasso, Italy; Integrated Access, Roche, Monza, Italy; Department of Oncology and Hemato-Oncology, University of Milano, Via Festa del Perdono, 7, 20122 Milano, ItalyBackground: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score. Results: A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions. Conclusions: The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA.http://www.sciencedirect.com/science/article/pii/S1936523323002553Liquid biopsyNGSNSCLCPredictive biomarkersResistance to treatment |
| spellingShingle | Marzia Del Re Giovanna Irene Luculli Iacopo Petrini Andrea Sbrana Vieri Scotti Diego de Miguel Perez Lorenzo Livi Stefania Crucitta Mauro Iannopollo Francesca Mazzoni Martina Ruglioni Carmelo Tibaldi Emanuela Olmetto Irene Stasi Editta Baldini Giacomo Allegrini Lorenzo Antonuzzo Franco Morelli Andrea Pierini Nicola Panzeri Stefano Fogli Antonio Chella Christian Rolfo Romano Danesi Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression Translational Oncology Liquid biopsy NGS NSCLC Predictive biomarkers Resistance to treatment |
| title | Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression |
| title_full | Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression |
| title_fullStr | Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression |
| title_full_unstemmed | Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression |
| title_short | Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression |
| title_sort | clinical utility of next generation sequencing of plasma cell free dna for the molecular profiling of patients with nsclc at diagnosis and disease progression |
| topic | Liquid biopsy NGS NSCLC Predictive biomarkers Resistance to treatment |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323002553 |
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