Next-Generation Sequencing to uncover the pre-clinical evolution of multiple myeloma

Niccolò Bolli Md-PhD
Dipartimento di Oncologia Medica ed Ematologia
Fondazione IRCCS Istituto Nazionale dei Tumori


Multiple myeloma (MM) is a neoplasm deriving from post-germinal centre B-lymphocytes that clonally evolve through different pre-clinical and pre-malignant stages. At diagnosis, multiple myeloma is a heterogeneous disease, and outgrowth of small sub clones is often observed in cases that relapse after treatment. Similarly, pre-malignant stages of MM are characterised by substantial heterogeneity, and analysis of spontaneous evolution show a similar pattern of branching of small sub clones.

Next-generation sequencing (NGS) of the genome allows for quantitative estimates of the percentage of cells that carry copy-number abnormalities and DNA mutations, information that can be used to re-construct the phylogenetic tree of the developing cancer. Furthermore, in duplicated chromosomes, analysis of the number of mutations acquired before and after the amplification can provide information on the timing of each duplication, assuming a constant mutational rate. Finally, mutations can be categorised based on the mutational process that caused them, and analysis of how these mutational processes act over time may shed some light on the pathogenesis of MM.

During the talk, I will present mostly unpublished work resulting from the application of mathematical models to the field of MM genomics, to infer biologically and clinically relevant information how it develops, evolves, and relapses after treatment.