Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response ultimate...
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/2911 |
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| author | Natalia Buenache Andrea Sánchez-delaCruz Isabel Cuenca Alicia Giménez Laura Moreno Joaquín Martínez-López Juan Manuel Rosa-Rosa |
| author_facet | Natalia Buenache Andrea Sánchez-delaCruz Isabel Cuenca Alicia Giménez Laura Moreno Joaquín Martínez-López Juan Manuel Rosa-Rosa |
| author_sort | Natalia Buenache |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response ultimately relapse. The earlier detection of tumor-related clonal DNA would thus be very beneficial for patients with MM and would enable timely therapeutic interventions to improve outcomes. Liquid biopsy of “cell-free DNA” (cfDNA) as a minimally invasive approach might be more effective than BM aspiration not only for the diagnosis but also for the detection of early recurrence. Most studies thus far have addressed the comparative quantification of patient-specific biomarkers in cfDNA with PPCs and BM samples, which have shown good correlations. However, there are limitations to this approach, such as the difficulty in obtaining enough circulating free tumor DNA to achieve sufficient sensitivity for the assessment of minimal residual disease. Herein, we summarize current data on methodologies to characterize MM, and we present evidence that targeted capture hybridization DNA sequencing (tchDNA-Seq) can provide robust biomarkers in cfDNA, including immunoglobulin (IG) rearrangements. We also show that detection can be improved by prior purification of the cfDNA. Overall, liquid biopsies of cfDNA to monitor IG rearrangements have the potential to provide important diagnostic, prognostic, and predictive information in patients with MM. |
| first_indexed | 2024-03-11T03:10:16Z |
| format | Article |
| id | doaj.art-247d72d0a37a414eb68f8fdad319df6d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:16Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-247d72d0a37a414eb68f8fdad319df6d2023-11-18T07:38:12ZengMDPI AGCancers2072-66942023-05-011511291110.3390/cancers15112911Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-SeqNatalia Buenache0Andrea Sánchez-delaCruz1Isabel Cuenca2Alicia Giménez3Laura Moreno4Joaquín Martínez-López5Juan Manuel Rosa-Rosa6Department of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainDepartment of Translational Haematology, Research Institute Hospital 12 de Octubre (i+12) Haematological Tumors Clinical Research Unit H12O-CNIO, 28041 Madrid, SpainMultiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response ultimately relapse. The earlier detection of tumor-related clonal DNA would thus be very beneficial for patients with MM and would enable timely therapeutic interventions to improve outcomes. Liquid biopsy of “cell-free DNA” (cfDNA) as a minimally invasive approach might be more effective than BM aspiration not only for the diagnosis but also for the detection of early recurrence. Most studies thus far have addressed the comparative quantification of patient-specific biomarkers in cfDNA with PPCs and BM samples, which have shown good correlations. However, there are limitations to this approach, such as the difficulty in obtaining enough circulating free tumor DNA to achieve sufficient sensitivity for the assessment of minimal residual disease. Herein, we summarize current data on methodologies to characterize MM, and we present evidence that targeted capture hybridization DNA sequencing (tchDNA-Seq) can provide robust biomarkers in cfDNA, including immunoglobulin (IG) rearrangements. We also show that detection can be improved by prior purification of the cfDNA. Overall, liquid biopsies of cfDNA to monitor IG rearrangements have the potential to provide important diagnostic, prognostic, and predictive information in patients with MM.https://www.mdpi.com/2072-6694/15/11/2911liquid biopsyIG rearrangementstchDNAseq |
| spellingShingle | Natalia Buenache Andrea Sánchez-delaCruz Isabel Cuenca Alicia Giménez Laura Moreno Joaquín Martínez-López Juan Manuel Rosa-Rosa Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq Cancers liquid biopsy IG rearrangements tchDNAseq |
| title | Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq |
| title_full | Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq |
| title_fullStr | Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq |
| title_full_unstemmed | Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq |
| title_short | Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq |
| title_sort | identification of immunoglobulin gene rearrangement biomarkers in multiple myeloma through cfdna based liquid biopsy using tchdna seq |
| topic | liquid biopsy IG rearrangements tchDNAseq |
| url | https://www.mdpi.com/2072-6694/15/11/2911 |
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