Table 3.

Summary of circulating tumor nucleic acids in bone and soft tissue sarcomas.

Sarcoma subtype	Circulating nucleic acid	Molecular target	Analysis method	Sample	Diagnostic value	Prognostic assessment	Response to therapy	Reference
OS	ctDNA	TP53,ATRX,DLG2,andMET mutations	tNGS	Plasma		√		64
		Chrosome 8q	ddPCR+NGS	Plasma		√		59
OS	ctRNA	miR-542-3p	RT-qPCR	Serum	√	√		79
		miR-221	RT-qPCR	Serum	√	√		80
		miR-191	RT-qPCR	Serum	√	√		81
		miR-124	RT-qPCR	Serum	√	√		83
		miR-421	RT-qPCR	Serum	√	√	√	82
		miR-25-3p	RT-qPCR	Serum	√	√	√	84
		miR-21	RT-qPCR	Serum		√	√	85
		miR-491	RT-qPCR	Serum		√		87
		miR-101	RT-qPCR	Serum		√		89
		miR-497	RT-qPCR	Serum		√		90
OS	ctRNA	miR-195	RT-qPCR	Serum		√	√	88
		miR-375	RT-qPCR	Serum		√	√	91
		miR133b and miR-206	RT-qPCR	Serum	√	√	√	92
		miR199a-3p, miR-21 and miR-143	RT-qPCR	Serum	√	√		93
		miR-215-5p andmiR-642a-5p	RT-qPCR	Serum		√		94
		miR-21, miR-221 and miR-106a	RT-qPCR	Serum		√		95
		miR-106a-5p, miR16-5p, miR-20a-5p, miR-425-5p, miR451a, miR-25-3P and miR139-5p	RT-qPCR	Serum		√	√	96
OS	ctRNA	lncRNA TUG1	RT-qPCR	Whole blood		√		111
		LncRNA UCA1	RT-qPCR	Plasma		√		112
ES	ctDNA	STAG2 and TP53	NGS	Plasma			√	59, 118
		EWS/FLI and EWS/ERG fusion sequences	dPCR	Plasma		√	√	18, 59, 63
		mtDNA	RT-qPCR	Serum	√	√		126
ES	ctRNA	EWS/FLI1 and EWS/ERG transcripts	RT-qPCR	Plasma		√	√	119-122
		miR-125b	RT-qPCR	Serum	√			127
CS	ctDNA	mutant IDH1/IDH2	dPCR	Plasma	√	√		133
LPS	ctDNA	TERT C228T break point t(12:16)	qPCR	Plasma		√		60
		TP53	NGS	Plasma			√	147
	ctRNA	miR-3613-3p	RT-qPCR	Whole blood		√		149
SS	ctDNA	SYT-SSX fusion sequence	Nested PCR	Peripheral blood			√	150-152
	ctRNA	miR-92b-3p	RT-qPCR	Serum	√	√	√	155
		miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p	RT-qPCR	Serum		√	√	56
RMS	ctDNA	PAX3-FOXO1 fusion	ddPCR	Plasma		√	√	159, 160
		miR-1, miR-133a, miR-133b and miR-206	RT-qPCR	Serum	√			162
LMS	ctDNA	TP53, RB1 and PTEN	ULP-WGS	Plasma		√		166
	ctDNA	TP53, PIK3CA and HRAS	tNGS	Plasma		√		50
	ctRNA	miR-199b-5p, miR-320a, miR-199a-3p, miR-126, andmiR-22	RT-qPCR	Plasma	√	√		170
GIST	ctDNA	KIT or PDGFRA	L-PCR or dPCR	Plasma	√	√	√	174-180

Abbreviations: tNGS: targeted next generation sequencing; cNGS: custom next generation sequencing; L-NGS: ligation-next generation sequencing; ULP-WGS: ultra-low passage whole-genome sequencing; ddPCR: droplet-digital polymerase chain reaction; dPCR: digital polymerase chain reaction; RT-qPCR: real time quantitative polymerase chain reaction; L-PCR: ligation-polymerase chain reaction