Genomic Sequencing Provides Insight into Myeloma Precursors

A study published in Nature Communications compared whole-genome sequencing between multiple myeloma (MM) and two precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SM).

For this study, investigators from the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine evaluated the whole genome sequence profile of 18 patients with MGUS and compared them to 14 patients with SM and 80 patients with MM. The team assessed a variety of genetic variations, including insertions, deletions, and driver gene mutations. Patients were followed for more than a year to monitor disease progression. The researchers found that patients with MGUS and a lighter mutational load were less likely to progress to MM.

“Most patients with MGUS will never progress, but some will,” said Ola Landgren, MD, professor of medicine, chief of the Myeloma Service, and principal investigator (PI) of the Myeloma Genomic Laboratory at Sylvester, via press release. “Using modern genomic assays and analytical algorithms, we are able to split the older terminology of MGUS and define progressors versus non-progressors.”

Prior to this study, according to the authors, it was believed that disease progression for MM was linear from MGUS to SM to MM. The non-progressive, clinically stable precursor condition, which was identified in 15 patients, was marked by later initiation in the patient’s life and the absence of certain myeloma-defining genomic events, such as chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity.

“The bigger picture is that there are several genomic defining events involved in the progression of MM,” said Francesco Maura, MD, assistant professor and co-PI of the Myeloma Genomic Laboratory. “So far, whole genome sequencing is the only technology that captures all these changes.”