Multiple myeloma progression: largest genome sequencing project of precursor offers insight
Researchers from the Dana-Farber Cancer Institute (MA, USA) have conducted the largest genomic analysis of patients with smoldering multiple myeloma (SMM) to date. SMM is an asymptomatic precursor to multiple myeloma. The results from this study, presented recently at the 59th American Society of Hematology Annual Meeting and Exposition (9–12 December, 2017, GA, USA), are believed to offer a new insight into the biological mechanism that occurs which causes this asymptomatic stage to develop into the symptomatic disease.
The team of researchers, led by Irene Ghobrial, sequenced 186 bone marrow biopsies from patients with SMM, some of whom progressed to multiple myeloma and some of whom did not. The team continued by matching the genomic data with standard analyses of risks of progression provided by current non-genetic clinical biomarkers.
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Mark Bustoros, a member of the research team, explained: “We found that mutations were more frequent in the high-risk group of patients with SMM. We also found that certain mutations that are known to be drivers for cancer progression were more enriched in that group.”
The mutations reported were commonly discovered among genes in the MAPK and NF-kB molecular pathways. Others were reported to be discovered in MYC gene aberrations, which are known to be altered in multiple myeloma. Patients who harbored these mutations were reported to be at a greater risk of progressing to the symptomatic disease.
In addition to analyzing bone marrow biopsies, the researchers sequenced 20 samples of cell-free DNA (cfDNA) in blood samples taken from patients with SMM. They reported the fractions of tumor DNA in the blood were higher in the high-risk SMM patients than in the low-risk SMM patients. The scientists hope to eventually develop methods to apply cfDNA sequencing to monitoring patients with myeloma and, especially its precursor conditions, Monoclonal Gammopathy of Undetermined Significance and SMM.
Samples for the research came from Dana-Farber’s Center for Prevention of Progression of Blood Cancers, which has gathered tissue and blood samples from more than 1000 patients with precursor conditions to various blood cancers. The researchers are now continuing their research by sequencing additional samples from further cancer centers from around the globe. The team also intend to analyze samples taken at different stages of myeloma progression.
Bustoros concluded: “After finishing the study, we will integrate genomic and clinical data and try to construct a model that can be applied in the clinic, to identify patients who are at high risk of progression, and potentially to offer them earlier treatment.”
Sources:
Bustoros M, Jihye P, Salem KZ et al. Next Generation Sequencing Identifies Smoldering Multiple Myeloma Patients with a High Risk of Disease Progression. Presented at: 59th American Society of Hematology (ASH) Annual Meeting and Exposition. GA, USA, 9–12 December 2017. (Epub ahead of print); Eureka Alert press release
