Professional Documents
Culture Documents
eTable 3. Liquid Biopsy–Detected Mutations for the 323 Patients Enrolled in the Study
eFigure 2. Correlation of Tissue AF for the Targeted Mutation and Depth of RECIST
Response to Targeted Therapy in 10 Patients with Tissue and Plasma Available
This supplementary material has been provided by the authors to give readers
additional information about their work.
© 2018 American Medical Association. All rights reserved.
00091 N N/A WT Report WT Report
00092 N EGFR L858R 15.10 1.00 clonal
00092 N PDGFRA Y225C 0.60 0.04 subclonal
00094 S CCDC6‐RET Fusion 9.40 1.00 clonal
00094 S RET‐CCDC6 Fusion 7.70 0.82 clonal
00094 S RB1 H483H 4.50 0.48 clonal
00094 S PTEN T277K 2.90 0.31 clonal
00094 S CDKN2A G23G 0.80 0.09 subclonal
00096 N TP53 R175H 0.10 1.00 clonal
00098 N N/A WT Report WT Report
00100 N EGFR R334H 0.40 1.00 clonal
00101 N EGFR L858R 1.00 1.00 clonal
00101 N ALK I1522T 0.70 0.70 clonal
00101 N EGFR E709A 0.60 0.60 clonal
00101 N TP53 G244S 0.30 0.30 clonal
00101 N PIK3CA H1047R 0.20 0.20 clonal
00106 N EGFR R108K 6.10 1.00 clonal
00106 N EGFR G719S 5.00 0.82 clonal
00106 N TP53 N239S 2.20 0.36 clonal
00106 N PIK3CA E545K 1.80 0.30 clonal
00106 N FGFR2 R203C 0.80 0.13 subclonal
00107 N BRAF E24A 0.50 1.00 clonal
00107 N TP53 C238Y 0.10 0.20 clonal
00109 N STK11 E351K 0.20 1.00 clonal
00109 N ERBB2 R143Q 0.20 1.00 clonal
00111 N BRCA1 E597K 0.20 1.00 clonal
00112 N SMO G212C 1.70 1.00 clonal
00112 N FGFR2 P508L 0.20 0.12 subclonal
00113 N ATM E3007D 7.50 1.00 clonal
00113 N CTNNB1 S45P 0.40 0.05 subclonal
00113 N EGFR L858R 0.40 0.05 subclonal
00113 N EGFR T790M 0.30 0.04 subclonal
00113 N STK11 D284A 0.20 0.03 subclonal
00113 N RB1 S919R 0.10 0.01 subclonal
00116 N TP53 R282W 3.50 1.00 clonal
00116 N EGFR Exon19del 2.20 0.63 clonal
00118 N N/A WT Report WT Report
00120 N EGFR N1094T 0.20 1.00 clonal
00120 N TP53 G105V 0.20 1.00 clonal
00120 N ARID1A Q840* 0.20 1.00 clonal
00121 N PIK3CA E545K 1.60 1.00 clonal
00121 N KRAS G12R 0.80 0.50 clonal
00121 N CCND1 A16V 0.40 0.25 clonal
00122 N N/A WT Report WT Report
00123 N EGFR Exon19del 9.70 1.00 clonal
00123 N EGFR C797S 6.90 0.71 clonal
00123 N EGFR T790M 3.80 0.39 clonal
00123 N TP53 R175G 0.40 0.04 subclonal
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
00243 N N/A WT Report WT Report
00244 N EGFR L858R 10.20 1.00 clonal
00244 N TP53 R175H 3.50 0.34 clonal
00244 N APC T1556fs 2.00 0.20 clonal
00244 N EGFR T790M 1.60 0.16 subclonal
00245 N TP53 H193P 17.70 1.00 clonal
00245 N CTNNB1 V22L 14.70 0.83 clonal
00245 N MET T579S 14.30 0.81 clonal
00245 N EGFR E245D 8.30 0.47 clonal
00245 N CDKN2A L45F 7.40 0.42 clonal
00245 N PIK3CA E149K 0.30 0.02 subclonal
00246 N STK11 Exon5del 17.20 1.00 clonal
00246 N NRAS Q61K 12.00 0.70 clonal
00246 N TP53 L26I 10.10 0.59 clonal
00246 N JAK2 V617F 2.00 0.12 subclonal
00246 N KRAS Q61H 0.20 0.01 subclonal
00247 N FGFR2 P508S 0.80 1.00 clonal
00248 N EGFR Exon19del 0.90 1.00 clonal
00248 N EGFR T790M 0.60 0.67 clonal
00248 N TP53 K132R 0.30 0.33 clonal
00248 N CDKN2A Exon1ins 0.20 0.22 clonal
00249 N NF1 R1412K 2.50 1.00 clonal
00249 N TP53 R213* 2.10 0.84 clonal
00249 N NF1 R1612S 1.80 0.72 clonal
00249 N EGFR S1042R 0.50 0.20 clonal
00249 N KIT N130N 0.30 0.12 subclonal
00249 N KRAS R135K 0.20 0.08 subclonal
00250 N STK11 Y60* 0.40 1.00 clonal
00250 N BRAF M23V 0.40 1.00 clonal
00250 N ALK G1202G 0.20 0.50 clonal
00251 N N/A WT Report WT Report
00252 N EGFR S768I 2.30 1.00 clonal
00252 N EGFR G719C 2.20 0.96 clonal
00252 N CDK6 R214L 1.80 0.78 clonal
00252 N BRCA1 V1181I 1.10 0.48 clonal
00252 N TP53 Y220C 0.30 0.13 subclonal
00253 N EGFR T790M 1.50 1.00 clonal
00253 N EGFR L858R 0.90 0.60 clonal
00253 N EGFR C797S 0.90 0.60 clonal
00254 N TP53 Q136* 0.30 1.00 clonal
00254 N KRAS G12C 0.20 0.67 clonal
00255 N TERT Q73P 13.80 1.00 clonal
00255 N EGFR Exon19del 6.00 0.43 clonal
00255 N SMAD4 Exon9del 3.30 0.24 clonal
00255 N CTNNB1 S33C 2.70 0.20 clonal
00255 N MYC S265R 2.70 0.20 clonal
00255 N TP53 L93R 1.30 0.09 subclonal
00255 N CCND1 D25A 1.10 0.08 subclonal
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
© 2018 American Medical Association. All rights reserved.
eTable 4. Patient Characteristics
eFigure 1. Analysis of Mutations Detected in Plasma and/or Tissue NGS
A. Mutational profile as determined by plasma NGS for 323 patients (green =
insertions/deletions/fusions, blue = synonymous mutation, red = nonsynonymous mutation). B.
Comparison of mutation prevalence for the 10 most frequently detected mutations for 128
patients who had both plasma (gray bars) and tissue (black bars) NGS completed. C. Among the
128 patients, 31 had a therapeutically targetable mutation detected in both plasma and tissue.
Shown is a comparison of the tissue and plasma AFs (ρ = 0.40, P = .023). Four of the 27 patients
had both a driver and a resistance mutation detected, so 31 data points are shown in the figure.
A B
PTEN T is s u e
T P53
APC
EGFR P la s m a
BRCA1
KRAS
N F1
NF1
M ET M ET
P IK 3 C A P IK 3 C A
ST K 11 S TK 11
AR KRAS
A R ID 1 A TP 53
C D K N 2A EG FR
ALK
0
1
2
ER B B 2
BRAF % T o t a l M u t a t io n s D e t e c te d
RB1
A PC
BRCA1
FGFR2 in s /d e l/fu s io n s
PD GFRA
PTEN synonym ous C 100
CTNNB1
T i s s u e A ll e le F r a c t io n (% )
nonsynonym ous
SMAD4
K IT 80
M YC
ATM
60
BRCA2
N OTC H 1
GNAS 40
CC N E1
TERT 20
CCND1
© 2018 American Medical Association. All rights reserved.
eFigure 2. Correlation of Tissue AF for the Targeted Mutation and Depth of RECIST Response to
Targeted Therapy in 10 Patients with Tissue and Plasma Available
Among the 42 patients shown in Figure 3 for whom RECIST response was measured, 10 had the
targetable mutation detected in both plasma and tissue. Shown here is the correlation of tissue
AF for the targeted mutation and depth of RECIST response to targeted therapy (n = 10
patients; r = 0.216, P = .176).
60
% Change in Target Lesion
40
20 Mutations
Tissue AF
0 Ex19del (driver)
20 40 60 80 T790M (resistance)
-20 MET Exon14 skip
-40
-60 2500
2000
-80 1500
1000
-100 500
0
0 2 4 6 8