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

During the last decade, there has been an impressive progress in the
treatment modalities of multiple myeloma (MM). However, MM is still
an incurable disease and patients become refractory to treatment at
some point in the disease evolution. MM is characterized by a patchy
tumor infiltration pattern in the bone marrow, implicating that analysis
of single bone marrow samples can lead to an underestimation of the
genetic heterogeneity within the tumor. Current evidence suggests
that the (epi)genetic profile can have an important impact on
prognosis and therapy response in MM. For these reasons, there is a
need for a flexible tool for accurate, practical and serial sampling for
(epi) genetic profiling during the course of disease. We believe that
peripheral blood-based methods may be the solution to this and may
provide a more comprehensive approach to genetic characterization
compared to conventional bone marrow samples. We recently
discovered that somatic and germline variants are detectable in DNA
derived from plasma-derived extracellular vesicles (EV-DNA) in MM.
However, these observations were made on a small number of
patients and genes on a proof-of-principle basis. Therefore, I want to
confirm and expand these observations on a larger scale, comparing
cell free DNA, EV-DNA and DNA derived from Circulating Tumor
Cells (CTCs) with bone marrow-derived DNA, evaluating their
applicability as noninvasive biomarkers for (epi)genetic
characterization and disease follow-up.