P-338: Differential DNA Mutation Profiles in Multiple Myeloma Patients: Implications of PET/CT Findings

Introduction: The presence of focal lesions in positron emission tomography/computed tomography (PET/CT) scans is well-established as a predictive marker in patients with multiple myeloma (MM). However, there is a lack of knowledge regarding the genetic backgrounds of patients with focal lesions in PET/CT. This study aimed to investigate the DNA sequencing analysis in patients with MM and compare the differences in mutation profiles based on PET/CT results.

Methods: PET/CT results were determined by the number of focal lesions and the presence of diffuse lesions in the skeletal bone, assessed using the Deauville score. Positive PET/CT findings were defined as metabolic uptake higher than the liver background. Targeted DNA sequencing of 80 mutations was performed to analyze MM cells extracted from the bone marrow using next-generation sequencing (NGS).

Results: Sixteen newly diagnosed MM patients were enrolled in this study. The median age of the patients was 66 years (range: 49-76). Four patients had ISS stage I, six had stage II, and six had stage III. High-risk cytogenetics, including t(4;14), t(14;16), and del(17p), were identified in six patients (37.5%). Additionally, six patients exhibited amp(1q). Eight patients (50.0%) had more than three focal lesions on PET/CT (FL > 3), while five patients (31.2%) showed positive findings for diffuse lesions on PET/CT. Two patients encountered issues with trimming the fastq file, resulting in a final sequencing analysis of 14 patients using the Genome Analysis Tool Kit (GATK). The analysis revealed a total of 152 somatic mutations with an allele frequency (AF) >1%. The top 10 frequently identified genes were KMT2C (57%), NCOR1 (57%), PABPC1 (50%), ATM (36%), RPS3A (36%), EP300 (29%), HUWE1 (29%), TET2 (29%), TP53 (29%), and ACTG1 (21%). Notably, PABPC1 (6/8, 75%) and KMT2C (6/8, 75%) mutations were more common in patients with FL > 3, whereas patients with FL ≤ 3 exhibited a higher frequency of ATM gene (4/6, 67%) mutations. In patients without diffuse lesions, NCOR1 mutations were frequently observed.

Conclusions: We found that mutation distribution varied according to PET/CT results, with patients exhibiting FL > 3 showing a higher frequency of PABPC1 and KMT2C mutations. Further studies are warranted to gain a better understanding of the genetic background associated with positive PET/CT findings in MM.