High diffuse bone marrow uptake in 18 F-FDG PET/CT may reflect the diverse mutational characteristics of multiple myeloma

Abstract To explore the biological implications of PET/CT findings in multiple myeloma (MM), we investigated the mutational characteristics relevant to PET/CT findings using targeted DNA sequencing. Fourteen newly diagnosed patients with MM who underwent ¹⁸F-fluorodeoxyglucose PET/CT at their initial diagnosis were included. For sequencing, a customized panel that covered 80 mutations relevant to MM biology was used. Serial PET/CT and sequencing following first-line treatment were performed in seven patients. The most frequently identified mutant gene was ATM, followed by HUWE1, PABPC1, and TP53. Patients with high diffuse FDG uptake (high DU) in their bone marrow showed a higher tumor burden than those with low diffuse uptake (low DU), and they were likely to have an inferior overall survival. Mutations detected in high DU were associated with various oncogenic pathways relevant to the disease progression of MM. Notably, pathways involving epigenetic regulators were predominantly enriched in patients with high DU. In serial follow-ups, a patient with residual PET/CT findings showed the emergence of new mutations; however, those with complete resolution of PET/CT abnormalities demonstrated improved mutational characteristics. In conclusion, patients with high DU showed diverse mutational characteristics, which may reflect the heterogeneous nature of MM and contribute to inferior survival outcomes.