Tracking myeloma tumor DNA in peripheral blood

Johannes M Waldschmidt; Tushara Vijaykumar; Birgit Knoechel; Jens G Lohr

doi:10.1016/j.beha.2020.101146

Tracking myeloma tumor DNA in peripheral blood

Best Pract Res Clin Haematol. 2020 Mar;33(1):101146. doi: 10.1016/j.beha.2020.101146. Epub 2020 Jan 14.

Authors

Johannes M Waldschmidt¹, Tushara Vijaykumar², Birgit Knoechel³, Jens G Lohr⁴

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: jensg_lohr@dfci.harvard.edu.

Abstract

Over the past years, the emergence of liquid biopsy technologies has dramatically expanded our ability to assess multiple myeloma without the need for invasive sampling. Interrogation of cell-free DNA from the peripheral blood recapitulates the mutational landscape at excellent concordance with matching bone marrow aspirates. It can quantify disease burden and identify previously undetected resistance mechanisms which may inform clinical management in real-time. The convenience of sample acquisition and storage provides strong procedural benefits over currently available testing. Further investigations will have to define the role of cell-free DNA as a diagnostic measure by determining clinically relevant tumor thresholds in comparison to existing routine parameters. This review presents an overview of currently available assays and discusses the clinical value, potential and limitations of cell-free DNA technologies for the assessment of this challenging disease.

Keywords: Cell-free DNA; Early cancer detection; Genomic profiling; Liquid biopsy; MRD; Next-generation sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / blood
Biomarkers, Tumor / genetics*
Circulating Tumor DNA / blood
Circulating Tumor DNA / genetics*
GTP Phosphohydrolases / blood
GTP Phosphohydrolases / genetics
Gene Expression Profiling
Genome, Human*
High-Throughput Nucleotide Sequencing / methods
Humans
Liquid Biopsy / methods
Membrane Proteins / blood
Membrane Proteins / genetics
Multiple Myeloma / diagnosis*
Multiple Myeloma / drug therapy
Multiple Myeloma / genetics*
Multiple Myeloma / pathology
Mutation*
Neoplasm, Residual
Plasma Cells / drug effects
Plasma Cells / metabolism
Plasma Cells / pathology
Proto-Oncogene Proteins B-raf / blood
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins p21(ras) / blood
Proto-Oncogene Proteins p21(ras) / genetics
Recurrence
Tumor Suppressor Protein p53 / blood
Tumor Suppressor Protein p53 / genetics

Substances

Antineoplastic Agents
Biomarkers, Tumor
Circulating Tumor DNA
KRAS protein, human
Membrane Proteins
TP53 protein, human
Tumor Suppressor Protein p53
BRAF protein, human
Proto-Oncogene Proteins B-raf
GTP Phosphohydrolases
NRAS protein, human
Proto-Oncogene Proteins p21(ras)

Abstract

Publication types

MeSH terms

Substances

Grants and funding