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

To explore the biological implications of positron emission tomography/computed tomography (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 (FDG) PET/CT at diagnosis were retrospectively reviewed. Targeted sequencing was performed on their bone marrow samples using a customized panel covering 80 genes relevant to MM biology. In seven patients, serial PET/CT and sequencing were also conducted after firstline treatment.

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.

Patients with high DU showed diverse mutational characteristics, which may reflect the heterogeneous nature of MM and contribute to inferior survival outcomes.