Liquid biopsy was introduced to the oncology field with the promise of revolutionizing the management of cancer patients, minimizing the exposure to invasive procedures such as tissue biopsy, and providing reliable information regarding therapy response and detection of disease relapse. Despite the significant increase in the number of published studies on circulating tumor DNA (ctDNA) in the past years, the emphasis of most studies is on the development of new technologies or on the clinical utility of ctDNA. This leaves a clear gap of knowledge concerning the biology of ctDNA, such as the fundamental mechanisms through which DNA from tumor cells is released into the circulation. Moreover, considering that ctDNA analysis is now currently being applied in clinical practice, the need for rigorous quality control is arising, and with it the necessity to standardize procedures, from sample collection to data analysis. This review focuses on the main aspects of ctDNA, including approaches currently available to evaluate tumor genetics, as well as the points that still require improvement in order to make liquid biopsy a key player in precision medicine.

1.
Mandel
P
,
Metais
P
.
Les acides nucléiques du plasma sanguin chez l’homme
.
C R Seances Soc Biol Fil
.
1948
Feb
;
142
(
3-4
):
241
3
.
[PubMed]
0037-9026
2.
Leon
SA
,
Shapiro
B
,
Sklaroff
DM
,
Yaros
MJ
.
Free DNA in the serum of cancer patients and the effect of therapy
.
Cancer Res
.
1977
Mar
;
37
(
3
):
646
50
.
[PubMed]
0008-5472
3.
Leary
RJ
,
Sausen
M
,
Kinde
I
,
Papadopoulos
N
,
Carpten
JD
,
Craig
D
,
O’Shaughnessy
J
,
Kinzler
KW
,
Parmigiani
G
,
Vogelstein
B
,
Diaz
LA
,
Velculescu
VE
:
Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing.
Science translational medicine
2012
;4:162ra154-162ra154.
4.
Imamura
F
,
Uchida
J
,
Kukita
Y
,
Kumagai
T
,
Nishino
K
,
Inoue
T
, et al.
Monitoring of treatment responses and clonal evolution of tumor cells by circulating tumor DNA of heterogeneous mutant EGFR genes in lung cancer
.
Lung Cancer
.
2016
Apr
;
94
:
68
73
.
[PubMed]
0169-5002
5.
Lo
YM
,
Zhang
J
,
Leung
TN
,
Lau
TK
,
Chang
AM
,
Hjelm
NM
.
Rapid clearance of fetal DNA from maternal plasma
.
Am J Hum Genet
.
1999
Jan
;
64
(
1
):
218
24
.
[PubMed]
0002-9297
6.
Madhavan
D
,
Wallwiener
M
,
Bents
K
,
Zucknick
M
,
Nees
J
,
Schott
S
, et al.
Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis
.
Breast Cancer Res Treat
.
2014
Jul
;
146
(
1
):
163
74
.
[PubMed]
0167-6806
7.
Sozzi
G
,
Conte
D
,
Mariani
L
,
Lo Vullo
S
,
Roz
L
,
Lombardo
C
, et al.
Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients
.
Cancer Res
.
2001
Jun
;
61
(
12
):
4675
8
.
[PubMed]
0008-5472
8.
Bettegowda
C
,
Sausen
M
,
Leary
RJ
,
Kinde
I
,
Wang
Y
,
Agrawal
N
, et al.
Shih l M, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA, Jr.: detection of circulating tumor DNA in early- and late-stage human malignancies
.
Sci Transl Med
.
2014
;
6
:
224ra224
.1946-6234
9.
Thierry
AR
.
A Targeted Q-PCR-Based Method for Point Mutation Testing by Analyzing Circulating DNA for Cancer Management Care
.
Methods Mol Biol
.
2016
;
1392
:
1
16
.
[PubMed]
1064-3745
10.
Diehl
F
,
Li
M
,
Dressman
D
,
He
Y
,
Shen
D
,
Szabo
S
, et al.
Detection and quantification of mutations in the plasma of patients with colorectal tumors
.
Proc Natl Acad Sci USA
.
2005
Nov
;
102
(
45
):
16368
73
.
[PubMed]
0027-8424
11.
Jiang
P
,
Chan
CW
,
Chan
KC
,
Cheng
SH
,
Wong
J
,
Wong
VW
, et al.
Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients
.
Proc Natl Acad Sci USA
.
2015
Mar
;
112
(
11
):
E1317
25
.
[PubMed]
0027-8424
12.
Jahr
S
,
Hentze
H
,
Englisch
S
,
Hardt
D
,
Fackelmayer
FO
,
Hesch
RD
, et al.
DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells
.
Cancer Res
.
2001
Feb
;
61
(
4
):
1659
65
.
[PubMed]
0008-5472
13.
Mouliere
F
,
Robert
B
,
Arnau Peyrotte
E
,
Del Rio
M
,
Ychou
M
,
Molina
F
, et al.
High fragmentation characterizes tumour-derived circulating DNA
.
PLoS One
.
2011
;
6
(
9
):
e23418
.
[PubMed]
1932-6203
14.
Snyder
MW
,
Kircher
M
,
Hill
AJ
,
Daza
RM
,
Shendure
J
.
Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin
.
Cell
.
2016
Jan
;
164
(
1-2
):
57
68
.
[PubMed]
0092-8674
15.
Soo
J
,
Kurtz
DM
,
Jin
M
,
Scherer
F
,
Schroers-Martin
JG
,
Esfahani
MS
, et al.
Comparison of Circulating Tumor DNA Recovery from Plasma and Serum
.
Blood
.
2017
;
130
:
2756
2756
.0006-4971
16.
Park
JL
,
Kim
HJ
,
Choi
BY
,
Lee
HC
,
Jang
HR
,
Song
KS
, et al.
Quantitative analysis of cell-free DNA in the plasma of gastric cancer patients
.
Oncol Lett
.
2012
Apr
;
3
(
4
):
921
6
.
[PubMed]
1792-1074
17.
Molina-Vila
MA
,
de-Las-Casas
CM
,
Bertran-Alamillo
J
,
Jordana-Ariza
N
,
González-Cao
M
,
Rosell
R
.
cfDNA analysis from blood in melanoma
.
Ann Transl Med
.
2015
Nov
;
3
(
20
):
309
.
[PubMed]
2305-5839
18.
van Ginkel
JH
,
van den Broek
DA
,
van Kuik
J
,
Linders
D
,
de Weger
R
,
Willems
SM
, et al.
Preanalytical blood sample workup for cell-free DNA analysis using Droplet Digital PCR for future molecular cancer diagnostics
.
Cancer Med
.
2017
Oct
;
6
(
10
):
2297
307
.
[PubMed]
2045-7634
19.
Botezatu
I
,
Serdyuk
O
,
Potapova
G
,
Shelepov
V
,
Alechina
R
,
Molyaka
Y
, et al.
Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism
.
Clin Chem
.
2000
Aug
;
46
(
8 Pt 1
):
1078
84
.
[PubMed]
0009-9147
20.
Su
YH
,
Wang
M
,
Brenner
DE
,
Ng
A
,
Melkonyan
H
,
Umansky
S
, et al.
Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer
.
J Mol Diagn
.
2004
May
;
6
(
2
):
101
7
.
[PubMed]
1525-1578
21.
Pan
W
,
Gu
W
,
Nagpal
S
,
Gephart
MH
,
Quake
SR
.
Brain tumor mutations detected in cerebral spinal fluid
.
Clin Chem
.
2015
Mar
;
61
(
3
):
514
22
.
[PubMed]
0009-9147
22.
Togneri
FS
,
Ward
DG
,
Foster
JM
,
Devall
AJ
,
Wojtowicz
P
,
Alyas
S
, et al.
Genomic complexity of urothelial bladder cancer revealed in urinary cfDNA
.
Eur J Hum Genet
.
2016
Aug
;
24
(
8
):
1167
74
.
[PubMed]
1018-4813
23.
Xia
Y
,
Huang
CC
,
Dittmar
R
,
Du
M
,
Wang
Y
,
Liu
H
, et al.
Copy number variations in urine cell free DNA as biomarkers in advanced prostate cancer
.
Oncotarget
.
2016
Jun
;
7
(
24
):
35818
31
.
[PubMed]
1949-2553
24.
Perdomo
S
,
Avogbe
PH
,
Foll
M
,
Abedi-Ardekani
B
,
Facciolla
VL
,
Anantharaman
D
, et al.
Circulating tumor DNA detection in head and neck cancer: evaluation of two different detection approaches
.
Oncotarget
.
2017
Aug
;
8
(
42
):
72621
32
.
[PubMed]
1949-2553
25.
Lianidou
E
,
Alix-Panabières
C
.
Early detection of lung cancer based on DNA methylation analysis in sputum and plasma
.
Transl Cancer Res
.
2017
;
6
S1
:
S51
3
. 2218-676X
26.
De Mattos-Arruda
L
,
Mayor
R
,
Ng
CK
,
Weigelt
B
,
Martínez-Ricarte
F
,
Torrejon
D
, et al.
Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma
.
Nat Commun
.
2015
Nov
;
6
(
1
):
8839
.
[PubMed]
2041-1723
27.
Ramalingam
N
,
Jeffrey
SS
.
Future of Liquid Biopsies With Growing Technological and Bioinformatics Studies: Opportunities and Challenges in Discovering Tumor Heterogeneity With Single-Cell Level Analysis
.
Cancer J
.
2018
Mar/Apr
;
24
(
2
):
104
8
.
[PubMed]
1528-9117
28.
Cohen
PA
,
Flowers
N
,
Tong
S
,
Hannan
N
,
Pertile
MD
,
Hui
L
.
Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening
.
BMC Med
.
2016
Aug
;
14
(
1
):
126
.
[PubMed]
1741-7015
29.
Bartak
BK
,
Kalmar
A
,
Galamb
O
,
Wichmann
B
,
Nagy
ZB
,
Tulassay
Z
,
Dank
M
,
Igaz
P
,
Molnar
B
:
Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of Liquid Biopsy Analysis for Colorectal Cancer Detection.
Pathology oncology research : POR
2018
30.
Markus
H
,
Contente-Cuomo
T
,
Farooq
M
,
Liang
WS
,
Borad
MJ
,
Sivakumar
S
, et al.
Evaluation of pre-analytical factors affecting plasma DNA analysis
.
Sci Rep
.
2018
May
;
8
(
1
):
7375
.
[PubMed]
2045-2322
31.
Zonta
E
,
Nizard
P
,
Taly
V
.
Assessment of DNA Integrity, Applications for Cancer Research
.
Adv Clin Chem
.
2015
;
70
:
197
246
.
[PubMed]
0065-2423
32.
Han
X
,
Wang
J
,
Sun
Y
.
Circulating Tumor DNA as Biomarkers for Cancer Detection
.
Genomics Proteomics Bioinformatics
.
2017
Apr
;
15
(
2
):
59
72
.
[PubMed]
1672-0229
33.
Guttery
DS
,
Page
K
,
Hills
A
,
Woodley
L
,
Marchese
SD
,
Rghebi
B
, et al.
Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer
.
Clin Chem
.
2015
Jul
;
61
(
7
):
974
82
.
[PubMed]
0009-9147
34.
Gale
D
,
Lawson
AR
,
Howarth
K
,
Madi
M
,
Durham
B
,
Smalley
S
, et al.
Development of a highly sensitive liquid biopsy platform to detect clinically-relevant cancer mutations at low allele fractions in cell-free DNA
.
PLoS One
.
2018
Mar
;
13
(
3
):
e0194630
.
[PubMed]
1932-6203
35.
Bennett
CW
,
Berchem
G
,
Kim
YJ
,
El-Khoury
V
.
Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer
.
Oncotarget
.
2016
Oct
;
7
(
43
):
71013
35
.
[PubMed]
1949-2553
36.
Christensen
E
,
Nordentoft
I
,
Vang
S
,
Birkenkamp-Demtröder
K
,
Jensen
JB
,
Agerbæk
M
, et al.
Optimized targeted sequencing of cell-free plasma DNA from bladder cancer patients
.
Sci Rep
.
2018
Jan
;
8
(
1
):
1917
.
[PubMed]
2045-2322
37.
Dobnik
D
,
Štebih
D
,
Blejec
A
,
Morisset
D
,
Žel
J
.
Multiplex quantification of four DNA targets in one reaction with Bio-Rad droplet digital PCR system for GMO detection
.
Sci Rep
.
2016
Oct
;
6
(
1
):
35451
.
[PubMed]
2045-2322
38.
Perakis
S
,
Speicher
MR
.
Emerging concepts in liquid biopsies
.
BMC Med
.
2017
Apr
;
15
(
1
):
75
.
[PubMed]
1741-7015
39.
Sacher
AG
,
Paweletz
C
,
Dahlberg
SE
,
Alden
RS
,
O’Connell
A
,
Feeney
N
, et al.
Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer
.
JAMA Oncol
.
2016
Aug
;
2
(
8
):
1014
22
.
[PubMed]
2374-2437
40.
Whale
AS
,
Fernandez-Gonzalez
A
,
Gutteridge
A
,
Devonshire
AS
.
Control Materials and Digital PCR Methods for Evaluation of Circulating Cell-Free DNA Extractions from Plasma
.
Methods Mol Biol
.
2018
;
1768
:
45
65
.
[PubMed]
1064-3745
41.
Kwapisz
D
.
The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?
Ann Transl Med
.
2017
Feb
;
5
(
3
):
46
.
[PubMed]
2305-5839
42.
Qiagen: QIAGEN announces first-ever regulatory registration of a lung cancer companion diagnostic based on liquid biopsies.
2015
43.
Merker
JD
,
Oxnard
GR
,
Compton
C
,
Diehn
M
,
Hurley
P
,
Lazar
AJ
, et al.
Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review
.
J Clin Oncol
.
2018
Jun
;
36
(
16
):
1631
41
.
[PubMed]
0732-183X
44.
Heitzer
E
,
Ulz
P
,
Geigl
JB
.
Circulating tumor DNA as a liquid biopsy for cancer
.
Clin Chem
.
2015
Jan
;
61
(
1
):
112
23
.
[PubMed]
0009-9147
45.
Veldore
VH
,
Choughule
A
,
Routhu
T
,
Mandloi
N
,
Noronha
V
,
Joshi
A
, et al.
Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
.
Lung Cancer (Auckl)
.
2018
Jan
;
9
:
1
11
.
[PubMed]
1179-2728
46.
Sozzi
G
,
Conte
D
,
Leon
M
,
Ciricione
R
,
Roz
L
,
Ratcliffe
C
, et al.
Quantification of free circulating DNA as a diagnostic marker in lung cancer
.
J Clin Oncol
.
2003
Nov
;
21
(
21
):
3902
8
.
[PubMed]
0732-183X
47.
Shao
X
,
He
Y
,
Ji
M
,
Chen
X
,
Qi
J
,
Shi
W
, et al.
Quantitative analysis of cell-free DNA in ovarian cancer
.
Oncol Lett
.
2015
Dec
;
10
(
6
):
3478
82
.
[PubMed]
1792-1074
48.
Hench
IB
,
Hench
J
,
Tolnay
M
.
Liquid Biopsy in Clinical Management of Breast, Lung, and Colorectal Cancer
.
Front Med (Lausanne)
.
2018
Jan
;
5
:
9
.
[PubMed]
2296-858X
49.
Bartoloni
E
,
Ludovini
V
,
Alunno
A
,
Pistola
L
,
Bistoni
O
,
Crinò
L
, et al.
Increased levels of circulating DNA in patients with systemic autoimmune diseases: A possible marker of disease activity in Sjögren’s syndrome
.
Lupus
.
2011
Aug
;
20
(
9
):
928
35
.
[PubMed]
0961-2033
50.
Klein-Scory
S
,
Maslova
M
,
Pohl
M
,
Eilert-Micus
C
,
Schroers
R
,
Schmiegel
W
, et al.
Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal Cancer
.
Transl Oncol
.
2018
Apr
;
11
(
2
):
213
20
.
[PubMed]
1936-5233
51.
Provencio
M
,
Torrente
M
,
Calvo
V
,
Pérez-Callejo
D
,
Gutiérrez
L
,
Franco
F
, et al.
Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients
.
Oncotarget
.
2017
Nov
;
9
(
1
):
488
94
.
[PubMed]
1949-2553
52.
Chu
D
,
Paoletti
C
,
Gersch
C
,
VanDenBerg
DA
,
Zabransky
DJ
,
Cochran
RL
, et al.
ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients
.
Clin Cancer Res
.
2016
Feb
;
22
(
4
):
993
9
.
[PubMed]
1078-0432
53.
Schiavon
G
,
Hrebien
S
,
Garcia-Murillas
I
,
Cutts
RJ
,
Pearson
A
,
Tarazona
N
, et al.
Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer
.
Sci Transl Med
.
2015
Nov
;
7
(
313
):
313ra182
.
[PubMed]
1946-6234
54.
Schøler
LV
,
Reinert
T
,
Ørntoft
MW
,
Kassentoft
CG
,
Árnadóttir
SS
,
Vang
S
, et al.
Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer
.
Clin Cancer Res
.
2017
Sep
;
23
(
18
):
5437
45
.
[PubMed]
1078-0432
55.
Germano
G
,
Mauri
G
,
Siravegna
G
,
Dive
C
,
Pierce
J
,
Di Nicolantonio
F
, et al.
Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in Metastatic Colorectal Cancer
.
Clin Colorectal Cancer
.
2018
Mar
;
17
(
1
):
80
3
.
[PubMed]
1533-0028
56.
Hu
W
,
Yang
Y
,
Zhang
L
,
Yin
J
,
Huang
J
,
Huang
L
, et al.
Post surgery circulating free tumor DNA is a predictive biomarker for relapse of lung cancer
.
Cancer Med
.
2017
May
;
6
(
5
):
962
74
.
[PubMed]
2045-7634
57.
Heitzer
E
,
Perakis
S
,
Geigl
JB
,
Speicher
MR
: The potential of liquid biopsies for the early detection of cancer. npj Precision Oncology
2017
;1:36.
58.
Remon
J
,
Menis
J
,
Hasan
B
,
Peric
A
,
De Maio
E
,
Novello
S
, et al.
The APPLE Trial: Feasibility and Activity of AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients. EORTC 1613
.
Clin Lung Cancer
.
2017
Sep
;
18
(
5
):
583
8
.
[PubMed]
1525-7304
59.
Knebel
FH
,
Bettoni
F
,
Shimada
AK
,
Cruz
M
,
Alessi
JV
,
Negrão
MV
, et al.
Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC
.
Lung Cancer
.
2017
Jun
;
108
:
238
41
.
[PubMed]
0169-5002
60.
Sun
Q
,
Liu
Y
,
Liu
B
,
Liu
Y
.
Use of Liquid Biopsy in Monitoring Colorectal Cancer Progression Shows Strong Clinical Correlation
.
Am J Med Sci
.
2018
Mar
;
355
(
3
):
220
7
.
[PubMed]
0002-9629
61.
Kang
S
,
Li
Q
,
Chen
Q
,
Zhou
Y
,
Park
S
,
Lee
G
, et al.
CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA
.
Genome Biol
.
2017
Mar
;
18
(
1
):
53
.
[PubMed]
1474-7596
62.
Marquard
AM
,
Birkbak
NJ
,
Thomas
CE
,
Favero
F
,
Krzystanek
M
,
Lefebvre
C
, et al.
TumorTracer: a method to identify the tissue of origin from the somatic mutations of a tumor specimen
.
BMC Med Genomics
.
2015
Oct
;
8
(
1
):
58
.
[PubMed]
1755-8794
63.
Cohen
JD
,
Li
L
,
Wang
Y
,
Thoburn
C
,
Afsari
B
,
Danilova
L
, et al.
Detection and localization of surgically resectable cancers with a multi-analyte blood test
.
Science
.
2018
Feb
;
359
(
6378
):
926
30
.
[PubMed]
0036-8075
64.
van Krieken
JH
,
Normanno
N
,
Blackhall
F
,
Boone
E
,
Botti
G
,
Carneiro
F
, et al.
Guideline on the requirements of external quality assessment programs in molecular pathology
.
Virchows Arch
.
2013
Jan
;
462
(
1
):
27
37
.
[PubMed]
0945-6317
65.
Shen
W
,
Zhao
GQ
,
Liang
Z
,
Yellapantula
V
,
Sun
S
,
Tang
LF
, et al.
Retrospective analysis of circulating tumor DNA of archived plasma samples
.
J Clin Oncol
.
2016
;
34
15_suppl
:
e23175
23175
. 0732-183X
66.
Chan
BA
,
Hughes
BG
.
Targeted therapy for non-small cell lung cancer: current standards and the promise of the future
.
Transl Lung Cancer Res
.
2015
Feb
;
4
(
1
):
36
54
.
[PubMed]
2218-6751
67.
Sorber
L
,
Zwaenepoel
K
,
Deschoolmeester
V
,
Van Schil
PE
,
Van Meerbeeck
J
,
Lardon
F
, et al.
Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients
.
Lung Cancer
.
2017
May
;
107
:
100
7
.
[PubMed]
0169-5002
68.
Köhn
L
,
Johansson
M
,
Grankvist
K
,
Nilsson
J
.
Liquid biopsies in lung cancer-time to implement research technologies in routine care?
Ann Transl Med
.
2017
Jul
;
5
(
13
):
278
.
[PubMed]
2305-5839
69.
Pérez-Callejo
D
,
Romero
A
,
Provencio
M
,
Torrente
M
.
Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring
.
Transl Lung Cancer Res
.
2016
Oct
;
5
(
5
):
455
65
.
[PubMed]
2218-6751
70.
Cai
X
,
Janku
F
,
Zhan
Q
,
Fan
JB
.
Accessing Genetic Information with Liquid Biopsies
.
Trends Genet
.
2015
Oct
;
31
(
10
):
564
75
.
[PubMed]
0168-9525
71.
Qiagen: therascreen® EGFR RGQ PCR Kit Instructions for Use (Handbook).
2013
72.
Kim
SS
,
Choi
HJ
,
Kim
JJ
,
Kim
MS
,
Lee
IS
,
Byun
B
, et al.
Droplet digital PCR-based EGFR mutation detection with an internal quality control index to determine the quality of DNA
.
Sci Rep
.
2018
Jan
;
8
(
1
):
543
.
[PubMed]
2045-2322
73.
Rothé
F
,
Laes
JF
,
Lambrechts
D
,
Smeets
D
,
Vincent
D
,
Maetens
M
, et al.
Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer
.
Ann Oncol
.
2014
Oct
;
25
(
10
):
1959
65
.
[PubMed]
0923-7534
74.
Forshew
T
,
Murtaza
M
,
Parkinson
C
,
Gale
D
,
Tsui
DW
,
Kaper
F
, et al.
Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA
.
Sci Transl Med
.
2012
May
;
4
(
136
):
136ra68
.
[PubMed]
1946-6234
75.
Newman
AM
,
Bratman
SV
,
To
J
,
Wynne
JF
,
Eclov
NC
,
Modlin
LA
, et al.
An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
.
Nat Med
.
2014
May
;
20
(
5
):
548
54
.
[PubMed]
1078-8956
76.
Kinde
I
,
Wu
J
,
Papadopoulos
N
,
Kinzler
KW
,
Vogelstein
B
.
Detection and quantification of rare mutations with massively parallel sequencing
.
Proc Natl Acad Sci USA
.
2011
Jun
;
108
(
23
):
9530
5
.
[PubMed]
0027-8424
77.
Siravegna
G
,
Marsoni
S
,
Siena
S
,
Bardelli
A
.
Integrating liquid biopsies into the management of cancer
.
Nat Rev Clin Oncol
.
2017
Sep
;
14
(
9
):
531
48
.
[PubMed]
1759-4774
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