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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Oct 14

PMID 36230824

Authors

Robbe Heestermans

Wouter De Brouwer

Ken Maes

Isabelle Vande Broek

Freya Vaeyens

Catharina Olsen

Ben Caljon

Ann De Becker

Marleen Bakkus

Rik Schots

Ivan Van Riet

Affiliations

Soon will be listed here.

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.

Citing Articles

Therapeutically Harnessing Tumor Cell-Derived Extracellular Vesicles for Multiple Myeloma: Recent Advances and Future Perspectives.

Xiao S, Chen L, Chen Z, Li Q Pharmaceutics. 2024; 16(11).

PMID: 39598562 PMC: 11597712. DOI: 10.3390/pharmaceutics16111439.

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

Heestermans R, Schots R, De Becker A, Van Riet I Int J Mol Sci. 2024; 25(10).

PMID: 38791247 PMC: 11121516. DOI: 10.3390/ijms25105208.

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