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

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 c...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2022-10, Vol.14 (19), p.4901
Main Authors: Heestermans, Robbe, De Brouwer, Wouter, Maes, Ken, Vande Broek, Isabelle, Vaeyens, Freya, Olsen, Catharina, Caljon, Ben, De Becker, Ann, Bakkus, Marleen, Schots, Rik, Van Riet, Ivan
Format: Article
Language:English
Subjects:
Biomarkers
Biopsy
Bone marrow
Diagnosis
DNA fingerprinting
DNA sequencing
Genes
Genetic aspects
Genetic diversity
Health aspects
Leukemia
Methods
Multiple myeloma
Mutation
Mutation (Biology)
Patients
Peripheral blood
Plasma cells
Tumor cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14194901