Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a "static progression model", where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a "spontaneous evolution model", where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation.

Original publication

DOI

10.1038/s41467-018-05058-y

Type

Journal article

Journal

Nature communications

Publication Date

22/08/2018

Volume

9

Addresses

Department of Oncology and Hemato-Oncology, University of Milan, Milan, 20122, Italy.

Keywords

Humans, Multiple Myeloma, Disease Progression, Risk Factors, Gene Expression Profiling, Genomics, Gene Expression Regulation, Neoplastic, Mutation, Databases, Genetic, Aged, Middle Aged, Female, Male, Smoldering Multiple Myeloma