Blood · 2024
RAS/RAF landscape in monoclonal plasma cell conditions.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Schavgoulidze Anais, Corre Jill, Samur Mehmet Kemal, Mazzotti Celine, Pavageau Luka, Perrot Aurore, Cazaubiel Titouan, Leleu Xavier, Macro Margaret, Belhadj Karim, Roussel Murielle, Brechignac Sabine, Montes Lydia, Caillot Denis, Frenzel Laurent, Rey Philippe, Schiano de Colella Jean-Marc, Chalopin Thomas, Jacquet Caroline, Richez Valentine, Orsini-Piocelle Frederique, Fontan Jean, Manier Salomon, Martinet Ludovic, Sciambi Adam, Mohty Mohamad, Avet-Loiseau Herve
Аннотация
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.