Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study

Robbe Heestermans; Wouter De Brouwer; Ken Maes; Isabelle Vande Broek; Freya Vaeyens; Catharina Olsen; Ben Caljon; Ann De Becker; M.H.C. Bakkus; Rik Schots; Ivan Van Riet

doi:10.3390/cancers14194901

Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study

Robbe Heestermans, Wouter De Brouwer, Ken Maes, Isabelle Vande Broek, Freya Vaeyens, Catharina Olsen, Ben Caljon, Ann De Becker, M.H.C. Bakkus, Rik Schots, Ivan Van Riet

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

The analysis of bone marrow (BM) samples in multiple myeloma (MM) patients can lead to the underestimation of the genetic heterogeneity within the tumor. Blood-derived liquid biopsies may provide a more comprehensive approach to genetic characterization. However, no thorough comparison between the currently available circulating biomarkers as tools for mutation profiling in MM has been published yet and the use of extracellular vesicle-derived DNA for this purpose in MM has not yet been investigated. Therefore, we collected BM aspirates and blood samples in 30 patients with active MM to isolate five different DNA types, i.e., cfDNA, EV-DNA, BM-DNA and DNA isolated from peripheral blood mononucleated cells (PBMNCs-DNA) and circulating tumor cells (CTC-DNA). DNA was analyzed for genetic variants with targeted gene sequencing using a 165-gene panel. After data filtering, 87 somatic and 39 germline variants were detected among the 149 DNA samples used for sequencing. cfDNA showed the highest concordance with the mutation profile observed in BM-DNA and outperformed EV-DNA, CTC-DNA and PBMNCs-DNA. Of note, 16% of all the somatic variants were only detectable in circulating biomarkers. Based on our analysis, cfDNA is the preferable circulating biomarker for genetic characterization in MM and its combined use with BM-DNA allows for comprehensive mutation profiling in MM.

Original language	English
Article number	4901
Number of pages	16
Journal	Cancers
Volume	14
Issue number	19
DOIs	https://doi.org/10.3390/cancers14194901
Publication status	Published - 7 Oct 2022

Bibliographical note

Funding Information:
This study was funded by a grant from Kom op tegen Kanker and the UZ Brussel Foundation. The first author (R.H., MD) is the recipient of a PhD fellowship Strategic Basic Research (1SE9322N) of the Research Foundation Flanders (FWO).

Publisher Copyright:
© 2022 by the authors.

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

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10.3390/cancers14194901

Cite this

@article{14882c685e644565841c62e2ee634069,

title = "Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study",

abstract = "The analysis of bone marrow (BM) samples in multiple myeloma (MM) patients can lead to the underestimation of the genetic heterogeneity within the tumor. Blood-derived liquid biopsies may provide a more comprehensive approach to genetic characterization. However, no thorough comparison between the currently available circulating biomarkers as tools for mutation profiling in MM has been published yet and the use of extracellular vesicle-derived DNA for this purpose in MM has not yet been investigated. Therefore, we collected BM aspirates and blood samples in 30 patients with active MM to isolate five different DNA types, i.e., cfDNA, EV-DNA, BM-DNA and DNA isolated from peripheral blood mononucleated cells (PBMNCs-DNA) and circulating tumor cells (CTC-DNA). DNA was analyzed for genetic variants with targeted gene sequencing using a 165-gene panel. After data filtering, 87 somatic and 39 germline variants were detected among the 149 DNA samples used for sequencing. cfDNA showed the highest concordance with the mutation profile observed in BM-DNA and outperformed EV-DNA, CTC-DNA and PBMNCs-DNA. Of note, 16% of all the somatic variants were only detectable in circulating biomarkers. Based on our analysis, cfDNA is the preferable circulating biomarker for genetic characterization in MM and its combined use with BM-DNA allows for comprehensive mutation profiling in MM.",

author = "Robbe Heestermans and {De Brouwer}, Wouter and Ken Maes and {Vande Broek}, Isabelle and Freya Vaeyens and Catharina Olsen and Ben Caljon and {De Becker}, Ann and M.H.C. Bakkus and Rik Schots and {Van Riet}, Ivan",

note = "Funding Information: This study was funded by a grant from Kom op tegen Kanker and the UZ Brussel Foundation. The first author (R.H., MD) is the recipient of a PhD fellowship Strategic Basic Research (1SE9322N) of the Research Foundation Flanders (FWO). Publisher Copyright: {\textcopyright} 2022 by the authors. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.",

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doi = "10.3390/cancers14194901",

language = "English",

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AU - Heestermans, Robbe

AU - De Brouwer, Wouter

AU - Maes, Ken

AU - Vande Broek, Isabelle

AU - Vaeyens, Freya

AU - Olsen, Catharina

AU - Caljon, Ben

AU - De Becker, Ann

AU - Bakkus, M.H.C.

AU - Schots, Rik

AU - Van Riet, Ivan

N1 - Funding Information: This study was funded by a grant from Kom op tegen Kanker and the UZ Brussel Foundation. The first author (R.H., MD) is the recipient of a PhD fellowship Strategic Basic Research (1SE9322N) of the Research Foundation Flanders (FWO). Publisher Copyright: © 2022 by the authors. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

PY - 2022/10/7

Y1 - 2022/10/7

N2 - The analysis of bone marrow (BM) samples in multiple myeloma (MM) patients can lead to the underestimation of the genetic heterogeneity within the tumor. Blood-derived liquid biopsies may provide a more comprehensive approach to genetic characterization. However, no thorough comparison between the currently available circulating biomarkers as tools for mutation profiling in MM has been published yet and the use of extracellular vesicle-derived DNA for this purpose in MM has not yet been investigated. Therefore, we collected BM aspirates and blood samples in 30 patients with active MM to isolate five different DNA types, i.e., cfDNA, EV-DNA, BM-DNA and DNA isolated from peripheral blood mononucleated cells (PBMNCs-DNA) and circulating tumor cells (CTC-DNA). DNA was analyzed for genetic variants with targeted gene sequencing using a 165-gene panel. After data filtering, 87 somatic and 39 germline variants were detected among the 149 DNA samples used for sequencing. cfDNA showed the highest concordance with the mutation profile observed in BM-DNA and outperformed EV-DNA, CTC-DNA and PBMNCs-DNA. Of note, 16% of all the somatic variants were only detectable in circulating biomarkers. Based on our analysis, cfDNA is the preferable circulating biomarker for genetic characterization in MM and its combined use with BM-DNA allows for comprehensive mutation profiling in MM.

AB - The analysis of bone marrow (BM) samples in multiple myeloma (MM) patients can lead to the underestimation of the genetic heterogeneity within the tumor. Blood-derived liquid biopsies may provide a more comprehensive approach to genetic characterization. However, no thorough comparison between the currently available circulating biomarkers as tools for mutation profiling in MM has been published yet and the use of extracellular vesicle-derived DNA for this purpose in MM has not yet been investigated. Therefore, we collected BM aspirates and blood samples in 30 patients with active MM to isolate five different DNA types, i.e., cfDNA, EV-DNA, BM-DNA and DNA isolated from peripheral blood mononucleated cells (PBMNCs-DNA) and circulating tumor cells (CTC-DNA). DNA was analyzed for genetic variants with targeted gene sequencing using a 165-gene panel. After data filtering, 87 somatic and 39 germline variants were detected among the 149 DNA samples used for sequencing. cfDNA showed the highest concordance with the mutation profile observed in BM-DNA and outperformed EV-DNA, CTC-DNA and PBMNCs-DNA. Of note, 16% of all the somatic variants were only detectable in circulating biomarkers. Based on our analysis, cfDNA is the preferable circulating biomarker for genetic characterization in MM and its combined use with BM-DNA allows for comprehensive mutation profiling in MM.

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DO - 10.3390/cancers14194901

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SN - 2072-6694

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JF - Cancers

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ER -

Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study

Abstract

Bibliographical note

Access to Document

Other files and links

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FWOSB118: Tumor characterization and disease follow-up in multiple myeloma by (epi) genetic profiling using liquid biopsies

Een innovatieve, niet-invasieve strategie voor mutatieanalyse bij multipel myeloom: liquid biopsies op de weg naar gepersonaliseerde geneeskunde

Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities

Cite this

Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Projects

FWOSB118: Tumor characterization and disease follow-up in multiple myeloma by (epi) genetic profiling using liquid biopsies

Research output

Een innovatieve, niet-invasieve strategie voor mutatieanalyse bij multipel myeloom: liquid biopsies op de weg naar gepersonaliseerde geneeskunde

Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities

Cite this