In a sequencing study of 82 patients with smoldering multiple myeloma, there were fewer NRAS and FAM46C mutations and with fewer adverse translocations – del(1p), del(14q), del(16q), and del(17p) – compared with newly diagnosed multiple myeloma. KRAS mutations were associated with a shorter time to progression. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are mechanisms underlying the transition to multiple myeloma, which may be used to guide early therapeutic interventions.
Boyle EM, Deshpande S, Tytarenko R, et al. The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma. Nat Commun. 2021;12(1):293.