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RAS/RAF landscape in monoclonal plasma cell conditions
Anais Schavgoulidze1, Jill Corre1, Mehmet Kemal Samur2
1Myeloma Genomic Lab, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Blood
|April 21, 2024
Summary
RAS/RAF pathway mutations are common in multiple myeloma, but often occur as secondary events in different subclones. This suggests the RAS/RAF pathway may not be an ideal therapeutic target in plasma cell disorders.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple myeloma exhibits significant molecular heterogeneity.
- The RAS/RAF pathway is frequently mutated in plasma cell disorders, often as a subclonal event.
Purpose of the Study:
- To characterize the RAS/RAF mutation landscape in a large cohort of plasma cell disorder patients.
- To investigate the clonal architecture of RAS/RAF mutations using single-cell sequencing.
Main Methods:
- Analysis of next-generation sequencing data from over 10,000 patients with plasma cell disorders.
- Single-cell sequencing on 29 patients with multiple RAS/RAF mutations.
Main Results:
- Approximately 61% of patients presented with RAS/RAF mutations at diagnosis or relapse.
- RAS/RAF mutation frequencies were lower in presymptomatic cases.
- Mutations differed from those in solid tumors, with a higher proportion of Q61 mutations.
- Single-cell sequencing revealed mutations often occurred in distinct subclones, indicating ongoing mutational processes.
Conclusions:
- RAS/RAF pathway mutations are prevalent but often secondary in plasma cell disorders.
- The subclonal nature of these mutations suggests they may not be suitable targets for therapy or residual disease monitoring.
