Multiple Myeloma Coverage from Every Angle

Whole-Genome Sequencing May Offer Insights to Multiple Myeloma Precursor Conditions

By: Cordi Craig, MS
Posted: Tuesday, May 4, 2021

Unlike many other cancers, multiple myeloma is preceded by asymptomatic precursor conditions, known as either monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma. Only a small fraction of patients with MGUS will progress to multiple myeloma, yet approximately 60% of patients who exhibit smoldering myeloma will develop cancer within 10 years of initial diagnosis. According to a study published in Nature Communications, whole-genome sequencing may help to determine which patients with a multiple myeloma precursor condition will develop cancer. According to the investigators, these findings may ultimately shift how patients with precursor conditions are currently diagnosed and treated.

“The bigger picture is that there are several genomic defining events involved in the progression of multiple myeloma,” Francesco Maura, MD, of the University of Miami, stated in an institutional press release. “So far, whole-genome sequencing is the only technology that captures all these changes.”

The research team performed whole-genome sequencing to assess 18 patients with MGUS, 14 patients with smoldering myeloma, and 80 patients with multiple myeloma. Patients were tracked for more than a year.

The researchers identified 15 patients with a nonprogressing, clinically stable precursor condition. These cases appeared to be characterized by a later start in the patient’s life and by the absence of myeloma-defining genomic events, including chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. Thus, patients with lighter mutational loads appeared to be less likely to develop multiple myeloma. The data suggest that whole-genome sequencing may be capable of recognizing two biologically and clinically distinct myeloma precursor conditions that are either stable or progressive.

“The application of this technology in the clinic has the potential to significantly alter the management of individual patients but will require confirmation in larger studies,” the research team concluded.

Disclosure: The study authors reported no conflicts of interest.

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