Circulating cell-free DNA as an alternative gateway to the genetic features of multiple myeloma and as a surrogate marker for disease burden in multiple myeloma.
This research project explores the research hypothesis that circulating cell-free DNA(ccfDNA) can serve as a minimally-invasive substrate to remotely investigate the genome of the malignant plasma cells in multiple myeloma (MM). We will extensively validate the detection of copy number variations in ccfDNA, by paired analysis of DNA from purified plasma cells by FISH, arrayCGH and low pass sequencing by next-generation sequencing with a particular focus on genomic imbalances with prognostic significance e.g. deletions of chromosome 1q, deletions of 17p13 and hyperdiploidy and hypodiploidy. We will also assess whether the MM clonotype, the unique patient-specific rearrangement of the IGH locs in the plasma cell clone, can be detected and quantified in ccfDNA and whether the presence of the clonotype in ccfDNA is a useful marker for detection of minimal residual disease (MRD). We will explore also the relationship between the quantity of the plasma cell clonotype in ccfDNA and conventional markers of disease burden in multiple myeloma (paraprotein level, tumor cell fraction in the bone marrow) by sequential sampling of the patient cohort during and after therapy.