RAS/RAF landscape in monoclonal plasma cell conditions.
Anais SchavgoulidzeJill CorreMehmet Kemal SamurCeline MazzottiLuka PavageauAurore PerrotTitouan CazaubielXavier LeleuMargaret MacroKarim BelhadjMurielle RousselSabine BrechignacLydia MontesDenis CaillotLaurent FrenzelPhilippe ReyJean Marc Schiano De ColellaThomas ChalopinCaroline JacquetValentine RichezFrederique Orsini-PiocelleJean FontanSalomon ManierLudovic MartinetAdam SciambiMohamad MohtyHerve Avet-LoiseauPublished in: Blood (2024)
Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed >10 000 patients with different plasma cell disorders to describe the RAS/RAF landscape. In this large cohort of patients, almost 61% of the patients presented a RAS/RAF mutation at diagnosis or relapse, but much lower frequencies occurred in presymptomatic cases. Of note, the mutations were different from that observed in solid tumors (higher proportions of Q61 mutations). In 29 patients with 2 different mutations, we were able to perform single-cell sequencing, showing that in most cases, mutations occurred in different subclones, suggesting an ongoing mutational process. These findings suggest that the RAS/RAF pathway is not an attractive target, both on therapeutic and residual disease assessment points of view.
Keyphrases
- single cell
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- multiple myeloma
- rna seq
- wild type
- gene expression
- patient reported outcomes
- mesenchymal stem cells
- genome wide
- patient reported
- bone marrow
- copy number
- dna methylation
- single molecule
- circulating tumor
- free survival
- cell free