Abstract 513P
Background
Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of monoclonal neoplastic plasma cells. Despite the availability of new therapies, large number of patients still relapse. The increasing use of next generation sequencing (NGS) has shown that the mutation profile is related to the impact the patients’ outcome. However, due to the spatial genetic heterogeneity in the bone marrow (BM) compartment of MM patients, genetic assessment of a single bone marrow sample can lead incomplete interpretation and may not be able to provide enough information. Liquid biopsy is a method that analyzing genetic tumor profile of circulating tumor DNA (ctDNA) in the blood. ctDNA is expected to originate from tumor cells and blood is a cocktail of ctDNAs that can overcome the spatial genetic heterogeneity in MM patients. Here, we performed targeted-capture sequencing using bone marrow (BM) plasma cells and ctDNA of 40 MM cases.
Methods
A total of 40 MM patients were enrolled in a single center. DNA from CD138+ cells in BM were subjected to targeted-capture sequencing for 112genes and for 31 genes, respectively. We used a positional indexing sequencing (PiSeq) analysis method with high depth sequencing to increase the detection capability of NGS to below 1% of variant allele frequency (VAF).
Results
Mutations are detected in most of the patients, 94.4% (34/36) of BM samples and 78.9% (30/38) 0f ctDNAs. We detected 74 and 22 recurrently mutated genes in BM and ctDNA, respectively. We identified 24 and 13 driver genes in BM and ctDNA, respectively including KRAS, NRAS, BRAF and TP53. Clonal hematopoiesis (CH) associated mutations, particularly DNMT3A were frequently observed, not only in ctDNA but also in BM.
Conclusions
Our results indicate that both BM and ctDNA can detect mutations, but considering the VAF of the mutations, using CD138+ cells in BM might be preferred for confirming the genetic profile. However, it is noteworthy that even with a small panel targeting 31 genes in ctDNA, a significant number of driver gene mutations were identified. Further research on the correlation between ctDNA profiling and patient prognosis, especially regarding CH gene mutations, is needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Research Foundation of Korea.
Disclosure
J.J. Kim: Non-Financial Interests, Institutional, Funding: National Research Foundation of Korea. All other authors have declared no conflicts of interest.