Table 5 Cytogenetic, genetic, and transcriptional profiles of tumor DNA in samples from different regions (cfDNA, CMMCs, BM, or EM)
Samples | Methods | Observations | References |
|---|---|---|---|
NDMM and RRMM CMMC vs. BMPC | FISH | CMMCs reflected cytogenetic changes in BM clonal PCs and consisted of unique cytogenetic subclones of BM clonal PCs | [62] |
MM CMMC vs. BMPC | FISH | The status of 13q deletions was consistent with FISH results from paired BM clonal PCs | [42] |
SMM and NDMM CMMC vs. BMPC | FISH | The status of t (4;14), t (14;16), and 17p deletion in CMMCs were consistent with BM FISH results in 88%, 94%, and 94% of NDMM patients, and in 91%, 90%, and 80% of SMM patients | [39] |
MM CMMC vs. BMPC | Microarray CA and GEP | 1. The concordance of CA between BM clonal PCs and CMMCs was 100% 2. Unsupervised clustering correctly clustered GEP of BM clonal PCs and CMMCs in 9 of 12 cases | [69] |
NDMM CMMC vs. BMPC | WES Mutations and CNA | 1. 90% of mutations in CMMCs were present in BM. 93% of mutations and 100% of clonal mutations in BM were present in CMMCs 2. The concordance of arm-level CNAs between BM clonal PCs and CMMCs was 92% | [92] |
NDMM and RRMM CMMC vs. BMPC vs. EMPC | WES and microarray Mutations, CNA, and translocation | 1. High concordance in the mutational profiles of three spatially distributed tumor samples at the individual level 2. 68% of mutations were shared by all three clones. CMMCs carried mutations in 92% of genes in BM or EM clonal cells 3. 82% of sSNV, 95% of arm-level sCNA, and only 39% of translocation in BM clonal PCs was present in CMMCs | [37] |
MM (CMMC only) | scDNA-seq: CNA | CNA patterns were overall conserved with subclonal alterations at the individual level | [93] |
MM (CMMC only) | scDNA-seq: CNA | CNA profiling revealed frequent convergent alterations at the individual level | [94] |
MM CMMC vs. BMPC | scDNA-seq: CNA | 1. CNA patterns in CMMCs were consistent with those in paired BM clonal PCs 2. The single-cell CNA of CMMCs was highly correlated with cytogenetics in the BM evaluated by karyotyping and FISH | [52] |
MGUS, MM CMMC vs. BMPC | scDNA-seq: mutations scRNA-seq: translocation | 1. 100% of targeted mutations (e.g., NRAS, KRAS, BRAF, IRF4, and TP53) in BM clonal PCs were confirmed in CMMCs 2. Some recurrent mutations were more abundant in CMMCs than those in BM clonal PCs 3. Translocations in CMMCs were confirmed by FISH in the BM | [51] |
MM CMMC vs. BMPC | scRNA-seq | 1. The gene expression signatures of CMMCs highly reproduced the transcriptional states in BM clonal PCs 2. There were a few differential expressions likely resulting from different environments (e.g., CRIP1 and KLF6) | [64] |
MGUS, NDMM, and RRMM CMMC vs. BMPC | scRNA-seq Bulk RNA-seq Microarray | 1. A significant correlation was observed in gene expression between CMMCs and BM clonal PCs 2. Genes involved in cytoskeleton reorganization and actin filament binding, migration/invasiveness, cellular adhesion, inflammation, coagulation, and cholesterol homeostasis were overexpressed in CMMCs. Genes involved in cell cycle were downregulated in CMMCs 3. Pathways involved in inflammation, angiogenesis, hypoxia, apoptosis, and epithelial–mesenchymal transition were upregulated in CMMCs. Pathways involved in cell cycle were downregulated in CMMCs | [65] |
MM with EM CMMC vs. BMPC | scRNA-seq | 1. CMMCs and BM clonal PCs tended to cluster in the same cell type 2. CXCL7 and secretion-related genes were significantly upregulated in CMMCs compared with those in BM clonal PCs | [35] |
MM with EM CMMC vs. BMPC | scRNA-seq | S1PR2 was significantly upregulated in CMMCs compared with that in BM clonal PCs | [66] |
NDMM, RRMM cfDNA vs. BM | LB-seq Mutations | 1. 96% of mutations in BM clonal PCs were detected in paired cfDNA with high specificity (> 98%) 2. Mutant VAFs and the subclonal hierarchy of multiple mutations were highly concordant between cfDNA and BM | [3] |
NDMM, RRMM cfDNA vs. BM | OMD Mutations | 1. 24.2% of mutations (in KRAS, NRAS, BRAF, and TP53) detected in cfDNA were missed by a single-point BM biopsy 2. 38 of 97 mutations identified in BM clonal PCs were confirmed in matched cfDNA | [10] |
NDMM, RRMM cfDNA vs. BM | OMD and TAS Mutations | 1. More cfDNA-specific mutations (in KRAS, NRAS, BRAF, and TP53) were identified in RRMM cases than those in NDMM cases 2. The frequency of mutations in the DNA repair genes in cfDNA was significantly higher than those in BM clonal PCs, whereas the frequency of RAS–RAF pathway mutations was equivalent between cfDNA and BM clonal PCs | [78] |
RRMM cfDNA vs. BM | OMD Mutations | 1. A combination of cfDNA and BM clonal PCs detected more mutations (80%) than BM clonal PCs alone (60%) 2. 33%, 27%, and 40% of the total mutations were shared, BM-specific, and cfDNA-specific, respectively | [80] |
MM cfDNA vs. BM | ddPCR Mutations | 1. Mutations present in the BM clonal PCs was identified in cfDNA in 18 of 19 cases 2. 34/35 mutations present in the BM clonal PCs was identified in cfDNA | [75] |
MM cfDNA vs. BM | ddPCR Mutations | 1. The concordances of cfDNA and paired BM clonal PCs for KRAS Mx, NRAS Q61, and NRAS G12/G13 were all 100% 2. The concordance of cfDNA and paired BM clonal PCs for BRAF V600Mx was 76% 3. The positive rate of BRAF, KRAS, and NRAS mutations in the BM tumor cells (34%) was significantly lower than that in cfDNA (53%) | [79] |
MGUS, SMM, NDMM, RRMM cfDNA vs. CMMC vs. BM | WES ULP-WGS Mutation and CNA | 1. A strong correlation in the large CNAs was observed between matched cfDNA and CMMC and BMPCs 2. 99% of clonal mutations and 81% of CNAs in BM were identified in cfDNA and/or CMMCs. 83% of non-silent clonal mutations in BM were confirmed in cfDNA. 88% of non-silent clonal mutations in cfDNA were confirmed in BM. 96% of non-silent clonal mutations in cfDNA were confirmed in CMMCs, whereas 84% of non-silent clonal mutations in CMMCs were confirmed in cfDNA | [46] |
NDMM, RRMM cfDNA vs. BM | LP-WGS and WES Mutation and CNA | 1. Overall concordance of CNAs between cfDNA and BM was 90.5%. All mutations in driver genes were identified in both cfDNA and BM 2. 93% of clonal mutations in BM were confirmed in cfDNA. 91% of clonal mutations in cfDNA were confirmed in BM | [49] |
NDMM, RRMM cfDNA vs. BM | ULP-WGS CNA | 1. Overall concordance of CNAs between cfDNA and BM was 67%. 12% and 21% of CNAs were BM-specific and cfDNA-specific, respectively 2. The status of 1q21 gain and 17p13 deletion in cfDNA profiles were consistent with the results in BM clonal PCs in in 78% of cases | [48] |
SMM and MM cfDNA vs. BM | ULP-WGS and NGS Mutations and CNA | 1. Almost all the mutations identified in the BM clonal PCs were confirmed in cfDNA 2. The concordance of CNAs between cfDNA and BM clonal PCs was higher in MM cases (51%) than in MGUS and SMM cases (14%) | [56] |
MGUS, SMM, MM cfDNA vs. BM | NGS Mutations | 1. Recurrent genes (e.g., NRAS, KRAS, TP53, TRAF3, FAM46C, CYLD, DIS3, BRAF, and IRF4) were detected in cfDNA 2. 72% of mutations in BM were confirmed in cfDNA 3. cfDNA profiling detected 100% of mutations in the BM when VAF of mutations was ≥ 5% in BM | [57] |
RRMM cfDNA vs. BM | NGS Mutations | 1. The ratio between the SNV number in PC and in ctDNA was greater than 80% in more than half of the patients 2. Key driver gene mutations were exclusively detected in ctDNA in 48% of patients, which was likely to be missed in the BM | [76] |
NDMM (case) cfDNA vs. BM | NGS Mutations and CA | 1. t (11; 14) in BM clonal PCs was confirmed in cfDNA. Monosomy 13, which was suspicious positive in BM, was detected in cfDNA 2. The VAF of the mutation in KRAS was significantly lower in cfDNA than that in BM clonal PCs | [95] |
MM with/without EM cfDNA vs. BM vs. EM | NGS Mutations | 1. 66.67% and 31.25% of mutations in EM clonal PCs were detected in paired cfDNA and paired BM clonal PCs, respectively 2. Somatic mutation concordance was higher between cfDNA and EM clonal PCs (87.3%) than between BM and EM clonal PCs (62.1%) | [59] |
NDMM cfDNA vs. BM | NGS Mutations, translocation | 1. More than 50% of the mutated genes were shared between ctDNA and BM. Mutations with the highest VAF were shared 2. A positive correlation was observed in VAF between ctDNA and BM samples 3. The detection rate of translocation in ctDNA was consistent with the detection rate in BM | [73] |