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Table 2 Individually identified markers with detection ability in ctDNA

From: The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

No

Biomarker

Acronym

Cancer

DNA alteration

Assay type (qPCR, ddPCR, BEAMing, NGS, Other)

Size Cases (controls)

Plasma or Serum

Refs

1

14–3-3 sigma

14–3-3 s

Breast

Methylation

qPCR

106 (74)

Serum

[48]

2

absent in melanoma 1

AIM1; Beta/gamma crystallin domain-containing protein 1

Lung

Methylation

qPCR

76 (30)

Serum

[62]

3

ADAM: metallopeptidase with thrombospondin type 1 motif, 1

ADAMTS1

Pancreatic

Methylation

qPCR

42

Serum

[63]

4

Adenomatous Polyposis Coli

APC

Lung

Methylation

qPCR

76 (30)

Serum

[62]

CRC

Mutation

qPCR

33 (10)

Plasma

[64]

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

CRC

Mutation

qPCR

191

Plasma

[65]

CRC

Methylation

qPCR

33

Serum

[53]

CRC

Mutation

PCR

104

Serum

[66]

Ovarian

Methylation

qPCR

87 (62)

Serum

[67]

Renal

Methylation

PCR

35 (54)

Serum

[68]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

Lung

Methylation

qPCR

110 (50)

Plasma

[70]

Renal

Methylation

qPCR

27 (15)

Plasma

[71]

CRC

Methylation

PCR

60 (100)

Plasma

[72]

5

ALU repeat

Alu 115 bp

Breast

NA

qPCR

39 (49)

Plasma

[22]

Alu 247 bp

Pancreatic

NA

qPCR

73 (43)

Plasma

[73]

CRC

NA

qPCR

50 (35)

Plasma

[20]

Breast

NA

qPCR

293 (100)

Plasma

[19]

Thyroid

NA

qPCR

176 (19)

Plasma

[24]

CRC

NA

qPCR

104 (173)

Serum

[23]

6

basonuclin 1

BNC1

Pancreatic

Methylation

qPCR

42

Serum

[63]

7

BIN1

BIN1

Breast

Methylation

qPCR

76 (30)

Serum

[62]

8

BLU

BLU

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

9

BRAF

BRAF (V600E)

Melanoma

Mutation

qPCR

221

Both

[17]

Lung

Mutation

NGS

68 (107)

Plasma

[75]

LCH

Mutation

qPCR

30

Plasma

[76]

CRC

Mutation

qPCR

106

Plasma

[77]

Thyroid

Mutation

qPCR

77

Plasma

[78]

CRC

Mutation

BEAMing

503

Plasma

[21]

CRC

Mutation

qPCR

191

Plasma

[65]

10

BRCA1

BRCA1

Breast

Methylation

qPCR

89

Serum

[79]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

Ovarian

Methylation

PCR

50

Serum

[80]

Ovarian

Methylation

PCR

33 (33)

Plasma

[81]

11

CALCA

CALCA

Ovarian

Methylation

PCR

30 (30)

Plasma

[82]

12

CDH1

CDH1

Ovarian

Methylation

qPCR

87 (62)

Serum

[67]

13

CDH13

CDH13

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

Lung

Methylation

qPCR

110 (50)

Plasma

[70]

14

CDO1

CDO1

Various

Methylation

qPCR

150 (60)

Plasma

[83]

15

CHD1

CHD1

Lung

Methylation

qPCR

76 (30)

Serum

[62]

16

CST6

CST6

Breast

Methylation

qPCR

196 (37)

Plasma

[84]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

17

CHRM2

CHRM2

Gastric

Methylation

qPCR

58 (30)

Serum

[85]

18

CYCD2

CYCD2

CRC

Methylation

qPCR

30 (30)

Plasma

[86]

19

DAPK1

DAPK1

HNSCC

Methylation

PCR

40 (41)

Serum

[87]

20

DCC

DCC

Lung

Methylation

qPCR

76 (30)

Serum

[62]

21

DCLK1

DCLK1

Lung

Methylation

qPCR

65 (95)

Plasma

[88]

Lung

Methylation

qPCR

32 (8)

Plasma

[89]

22

DKK3

DKK3

Breast

Methylation

qPCR

604 (59)

Serum

[90]

23

DLEC1

DLEC1

Lung

Methylation

qPCR

110 (50)

Plasma

[70]

HNSCC

Methylation

PCR

40 (41)

Serum

[87]

24

DNA (NOS)

DNA

Lung

NA

qPCR v Seq

30 (26)

Plasma

[91]

Various

No

NGS

77 (35)

Plasma

[45]

Various

No

NGS

640

Plasma

[16]

Lung

No

qPCR

65 (44)

Plasma

[92]

Ovarian

No

bDNA

36 (41)

Serum

[93]

25

e-cadherin

e-cadherin

Colorectal

Methylation

PCR

60 (100)

Plasma

[72]

26

EGFR

EGFR

Lung

Mutation

NGS

68 (107)

Plasma

[75]

27

EP300

EP300

Ovarian

Methylation

PCR

30 (30)

Plasma

[82]

28

ERBB2

HER2

Lung

Mutation

NGS

68 (107)

Plasma

[75]

Breast

Amplification

qPCR

120 (98)

Plasma

[14]

Oesphageal

Amplification

qPCR

41 (34)

Plasma

[94]

29

ESR

ESR

Breast

Methylation

qPCR

106 (74)

Serum

[48]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

30

FAM5C

FAM5C

Gastric

Methylation

qPCR

58 (30)

Serum

[85]

31

FHIT

FHIT

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

Renal

Methylation

qPCR

27 (15)

Plasma

[71]

32

Glyceraldehyde-3-phosphate dehydrogenase

GAPDH

Breast

NA

qPCR

200 (100)

Serum

[26]

Breast

NA

qPCR

33 (50)

Serum

[27]

Breast

NA

qPCR

27 (32)

Serum

[28]

Breast

NA

qPCR

33 (32)

Serum

[29]

33

GNA11

GNA11

Uveal Melanoma

Mutation

NGS

28

Plasma

[34]

34

GNAQ

GNAQ

Uveal Melanoma

Mutation

NGS

28

Plasma

[34]

35

GPC3

GPC3

Pancreatic

Methylation

qPCR

30 (30)

Plasma

[86]

36

GSTP1

GSTP1

Breast

Methylation

qPCR

89

Serum

[79]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

Prostate

Methylation

PCR

12 (10)

Plasma

[95]

Prostate

Methylation

qPCR

31 (44)

Plasma

[96]

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

Renal

Methylation

PCR

35 (54)

Serum

[68]

Prostate

Methylation

PCR

31 (34)

Serum

[97]

37

HIC1

HIC1

CRC

Methylation

PCR

30 (30)

Plasma

[98]

CRC

Methylation

qPCR

30 (30)

Plasma

[86]

38

HOXA7

HOXA7

Various

Methylation

qPCR

150 (60)

Plasma

[83]

39

HOXA9

HOXA9

Various

Methylation

qPCR

150 (60)

Plasma

[83]

40

HOXD13

HOXD13

Breast

Methylation

qPCR

253 (434)

Serum

[99]

41

IgH

FR3A/VLJH

Lymphoma

Clonality

NGS

75

Plasma

[43]

42

ITIH5

 

Breast

Methylation

qPCR

604 (59)

Serum

[90]

43

INK4A

INK4A

HCC

Methylation

Seq

66 (43)

Plasma

[100]

44

KLK10

KLK10

Lung

Methylation

qPCR

110 (50)

Plasma

[70]

45

KRAS

KRAS

Lung

Mutation

NGS

68 (107)

Plasma

[75]

CRC

Mutation

qPCR

52

Plasma

[101]

CRC

Mutation

qPCR

35 (135)

Plasma

[30]

CRC

Mutation

qPCR

229 (100)

Plasma

[102]

CRC

Mutation

qPCR

106

Plasma

[77]

Lung

Mutation

qPCR

82 (11)

Plasma

[103]

CRC

Mutation

BEAMing

503

Plasma

[21]

CRC

Mutation

qPCR

191

Plasma

[65]

CRC

Mutation

PCR

104

Serum

[66]

46

LINE1 Repeat

LINE1 79 bp

CRC

NA

qPCR

50 (35)

Plasma

[20]

LINE1 300 bp

CRC

NA

qPCR

503

Plasma

[21]

Breast

NA

qPCR

293 (100)

Plasma

[19]

47

MDG1

MDG1

CRC

Methylation

PCR

30 (30)

Plasma

[98]

48

Microsatellite alterations

FHIT LoH

Lung

NA

PCR

87 (14)

Plasma

[104]

FHIT LoH

Lung

NA

PCR

32 (10)

Serum

[105]

LoH

Oesophageal

NA

PCR

18 (22)

Plasma

[106]

LoH

CRC

NA

qPCR

33

Serum

[53]

3p LoH

Lung

NA

qPCR

64

Plasma

[107]

49

mitochondrial DNA

mtDNA

Breast

NA

qPCR

60 (51)

Plasma

[108]

50

MLH1

hMLH1

Breast

Methylation

qPCR

253 (434)

Serum

[99]

51

MYC

MYC

Neuroblastoma

Amplification

ddPCR

44

Plasma

[42]

52

MYF3

MYF3

Pancreatic

Methylation

qPCR

30 (30)

Plasma

[86]

53

MYLK

MYLK

Gastric

Methylation

qPCR

58 (30)

Serum

[85]

54

O(6)-methyl-guanine-DNA methyltransferase

MGMT

Lung

Methylation

qPCR

76

Serum

[62]

CRC

Methylation

qPCR

33

Serum

[53]

Breast

Methylation

qPCR

89

Serum

[79]

55

OPCML

OPCML

Ovarian

Methylation

qPCR

87 (62)

Serum

[67]

56

P14 ARF tumor suppressor protein gene

P14

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

Renal

Methylation

PCR

35 (54)

Serum

[68]

57

P16 cyclin-dependent kinase inhibitor 2A

P16, CDKN2A

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

Renal

Methylation

PCR

35 (54)

Serum

[68]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

Breast

Methylation

qPCR

253 (434)

Serum

[99]

HNSCC

Methylation

qPCR

40 (41)

Serum

[87]

58

P21

P21

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

59

P53

 

Various

Mutation

qPCR

20 (16)

Plasma

[109]

Various

NA

qPCR

120 (120)

Plasma

[110]

CRC

Mutation

qPCR

191

Plasma

[65]

CRC

Mutation

PCR

104

Serum

[66]

SCLC

Mutation

qPCR

51 (123)

Plasma

[55]

60

PCDHGB7

PCDHGB7

Breast

Methylation

qPCR

253 (434)

Serum

[99]

61

Peptidylprolyl isomerase A

cyclophilin A, gCYC, PPIA

CRC

NA

qPCR

229 (100)

Plasma

[102]

62

PIK3CA

PIK3CA

Breast

Mutation

qPCR

76

Both

[18]

Lung

Mutation

NGS

68 (107)

Plasma

[75]

CRC

Mutation

BEAMing

503

Plasma

[21]

CRC

Mutation

qPCR

191

Plasma

[65]

63

Prostaglandin-endoperoxid synthase 2

PTGS2

Renal

Methylation

PCR

35 (54)

Serum

[68]

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

64

Protocadherin 10

PCDH10

CRC

Methylation

qPCR

67

Plasma

[111]

65

Retinoid-acid-receptor-beta gene

RARbeta2

Breast

Methylation

PCR

20 (25)

Plasma

[112]

CRC

Methylation

qPCR

33

Serum

[53]

Renal

Methylation

PCR

35 (54)

Serum

[68]

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

66

RASSF1A

RASSF1A

Breast

Methylation

PCR

93 (76)

Plasma

[113]

Breast

Methylation

PCR

20 (25)

Plasma

[112]

Breast

Methylation

qPCR

39 (49)

Plasma

[22]

Breast

Methylation

qPCR

604 (59)

Serum

[90]

Melanoma

Methylation

qPCR

84 (68)

Plasma

[114]

Lung

Methylation

qPCR

76 (30)

Serum

[62]

Testicular

Methylation

qPCR

73 (35)

Serum

[47]

CRC

Methylation

qPCR

33

Serum

[53]

Ovarian

Methylation

qPCR

87 (62)

Serum

[67]

Renal

Methylation

PCR

35 (54)

Serum

[68]

Lung

Methylation

qPCR

63 (36)

Plasma

[74]

Lung

Methylation

qPCR

110 (50)

Plasma

[70]

HCC

Methylation

PCR

40 (20)

Serum

[115, 116]

HCC

Methylation

PCR

50 (50)

Serum

[117]

Renal

Methylation

PCR

27 (15)

Plasma

[71]

Breast

Methylation

qPCR

253 (434)

Serum

[99]

CRC

Methylation

PCR

30 (30)

Plasma

[98]

Renal

Methylation

qPCR

157 (43)

Serum

[118]

Ovarian

Methylation

PCR

50

Serum

[80]

Ovarian

Methylation

PCR

30 (30)

Plasma

[82]

67

RUNX3

RUNX3

Ovarian

Methylation

PCR

87 (62)

Serum

[67]

68

Septin 9

Septin 9

CRC

Methylation

qPCR

97 (172)

Plasma

[119]

CRC

Methylation

qPCR

378 (285)

Plasma

[120]

CRC

Methylation

qPCR

60 (24)

Plasma

[121]

CRC

Methylation

qPCR

55 (1457)

Plasma

[58]

Lung

Methylation

qPCR

70 (100)

Plasma

[122]

CRC

Methylation

qPCR

135 (341)

Plasma

[123]

CRC

Methylation

qPCR

50 (94)

Plasma

[124]

CRC

Methylation

qPCR

44 (444)

Plasma

[59]

69

SFN

SFN

Breast

Methylation

qPCR

253 (434)

Serum

[99]

70

SFRP5

SFRP5

Ovarian

Methylation

qPCR

87 (62)

Serum

[67]

71

SHOX2

SHOX2

Lung

Methylation

qPCR

188 (155)

Plasma

[125]

Lung

Methylation

qPCR

118 (212

Plasma

[126]

72

SOX17

SOX17

Breast

Methylation

qPCR

114 (60)

Plasma

[127]

Various

Methylation

qPCR

150(60)

Plasma

[83]

73

SLC26A4

SLC26A4

Thyroid

Methylation

qPCR

176 (19)

Plasma

[24]

74

SLC5A8

SLC5A8 SLC26A4

Thyroid

Methylation

qPCR

176 (19)

Plasma

[24]

75

SRBC

SRBC

Pancreatic

Methylation

qPCR

30 (30)

Plasma

[86]

76

TAC1

TAC1

Various

Methylation

qPCR

150 (60)

Plasma

[83]

77

human telomerase reverse transcriptase DNA

hTERT

CRC

NA

qPCR

35 (135)

Plasma

[30]

HCC

NA

qPCR

70 (30)

Plasma

[31]

HCC

NA

qPCR

60 (29)

Plasma

[32]

HNSCC

NA

qPCR

200

Plasma

[33]

78

TFPI2

TFPI2

Ovarian

Methylation

PCR

87 (62)

Serum

[67]

79

THBD-M

THBD-M

CRC

Methylation

qPCR

107 (98)

Plasma & Serum

[128]

80

TIMP3

TIMP3

Renal

Methylation

PCR

35 (54)

Serum

[68]

Breast

Methylation

qPCR

36 (30)

Plasma

[69]

81

TMS

TMS

Pancreatic

Methylation

qPCR

30 (30)

Plasma

[86]

82

UCHL1

UCHL1

HNSCC

Methylation

PCR

40 (41)

Serum

[87]

83

Von Hippel Lindau gene

VHL

CRC

Methylation

qPCR

30 (30)

Plasma

[86]

Pancreatic

Methylation

qPCR

30 (30)

Plasma

[86]

Renal

Methylation

qPCR

157 (43)

Serum

[118]

84

ZFP42

ZFP42

Various

Methylation

qPCR

150 (60)

Plasma

[83]

  1. CRC colorectal cancer, HNSCC head and neck squamous cell carcinoma, HCC hepatocellular carcinoma, LCH Langerhans cell histocytosis, SCLC small cell lung cancer