Table 5.

Current status of various studies on the utility of ctDNA in molecular characterization of MM

S.No.	Title of Study	Genes Targets by ctDNA	Outcome	Reference
1	ctDNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates	Five genes (18 kb) (KRAS, NRAS, BRAF, EGFR, PIK3CA)	Ultra-deep sequencing of cfDNA to >20,000 × median coverage. Showed 96% concordance and >98% specificity when compared with matched BMA samples.	[12]
2	ctDNA analysis demonstrates spatial mutational heterogeneity that coincides with disease relapse in myeloma	Four genes (KRAS, NRAS, BRAF, TP53)	Mutations detected by OnTarget Mutation Detection (OMD) and ddPCR. High frequency of Plasma-Only mutations was observed in relapsed/refractory patients than newly diagnosed.	[13]
3	Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma	All genes and their exons	Screened and monitored tumor fraction and copy-number changes in cfDNA and CTCs using ultra-low pass whole-genome sequencing and whole-genome sequencing of matched CTCs, cfDNA and bone marrow biopsies from MM patients. ~99% concordance in clonal somatic mutations and ~81% concordance in copy number alterations between liquid and tumor biopsies.	[122]