Pb2094: application of whole-genome sequencing for copy number abnormality in multiple myeloma

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Copy number abnormalities (CAA) is an important prognosis factor for multiple myeloma (MM). The detection rate of existing detection methods is low and the chromosomal variation cannot be obtained comprehensively. LeukoPrint is a novel shallow whole-genome sequencing (sWGS) based approach to profile CNA may make up for the deficiencies of traditional detection techniques and improve the detection rate of chromosome variation. Aims: To observe the clinical application of sWGS in detecting chromosome copy number variation in patients with newly diagnosed multiple myeloma. Methods: A total of 131 patients with newly diagnosed multiple myeloma were enrolled in this study to compare the effectiveness of detection techniques among sWGS, Karyotyping, flurescence in situ hybridization (FISH). Karyotyping and FISH were performed by conventional approaches. CNA was detected by sWGS in genomic DNA from bone marrow aspiration samples and CD138+ enriched plasma cells as well as in plasma cfDNA. Risk stratification was performed following the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) criteria. Results: In this study, CNA events were identified by sWGS in 75.6% patients, while the positive rate of CNA detected by karyotyping and FISH was 7.8% and 43.7%, respectively. The most frequently mutational CNA peak region were amp(1q21),del(1p),del(6q), del(8p21.2), del(13q14),del(14q) and del(16p). The concordance rate between sWGS and FISH in detecting the four conventional loci (1q21 gain, 13q14 del, 13q14.3 del, and 17p13 del) was 80.2%. Comparing to the conventional approaches, sWGS provided new CNA information for 75.6% of the patients, and changed the risk stratification for 19.1% of patients according to mSMART criteria. sWGS showed good consistency the CNA detection between bone marrow and plasma cfDNA of 15 patients. Conclusion: sWGS is superior to conventional approaches when used for CNA testing, the practice of this method maybe improves prognostic stratification of MM patients and the clinical significance of some variation remains to be studied. Keywords: Multiple myeloma