. Author manuscript; available in PMC: 2019 May 1.

Published in final edited form as: Mol Cancer Ther. 2018 Feb 26;17(5):1114–1122. doi: 10.1158/1535-7163.MCT-17-0604

Table 2.

Risk factors, genomic alteration pattern, and percent ctDNA in 26 patients with HCC

Patient	Risk Factor	Tissue NGS/Molecular^**	Relative Date of Tissue NGS	Relative Date of Serial ctDNA	ctDNA Characterized Alterations (%ctDNA)	ctDNA VUS (%ctDNA)	AFP Levels (ng/mL) (Normal range, <15ng/ml)^***	Child-Pugh Score (Class)

1	HBV	N/A	N/A	Day 0^*	TP53 R249S 33.31%		>60500.0	11 (C)

2	HCV	N/A	N/A	Day 0	CTNNB1 D32N 0.22%	CTNNB1 S29T 0.23%	870	11 (C)
						EGFR D837Y 0.20%

3	HCV	TP53 H179P	Day 0	Day 828	TP53 H179P 37.77%	ARID1A A226P 1.11%	N/A	N/A
		ARID1A A226fs*5			BRAF amplification
					FGFR1 amplification
					CDK6 amplification
					EGFR amplification

4	HCV	TP53 R273C	Day 0	Day 460	MET Y501C 2.05%		13480	11 (C)
					PTEN L139* 0.21%
					TP53 R273C 1.18%

				Day 592	PTEN L139* 0.65%
					TP53 R273C 1.01%
					TP53 H179Y 0.18%
					EGFR E20fs 0.06%

				Day 624	PTEN L139* 0.15%
					TP53 R273C 1.63%
					TP53 H179Y 0.13%

5	HCV	N/A	N/A	Day 0	TP53 R175H 29.51%	ARID1A Q2207R 0.55%	374000	11 (C)
					CTNNB1 S33C 13.02%

6	HCV	N/A	N/A	Day 0	CDKN2A R80* 0.55%		10	9 (B)
					CTNNB1 G34V 1.35%

7	Metabolic Syndrome	AKT2 amplification	Day 0	Day 91	CCNE1 amplification		448100	6 (A)
	Metabolic Syndrome	CCNE1 amplification			CDK6 amplification
		CCNE1 amplification			PIK3CA amplification
		TP53 D281E			EGFR amplification
					MYC amplification

8	Metabolic Syndrome	N/A	N/A	Day 0	CTNNB1 H36P 12.09%	MAP2K1 V60M 0.67%	3	8 (B)
	Metabolic Syndrome				RAF1 I634F 0.12%	ATM R337C 0.27%
					TP53 H179R 0.13%	ALK R1347Q 0.12%
					RAF1 amplification

				Day 156	CTNNB1 H36P 31.54%	MAP2K1 V60M 0.35%
					TP53 R273H 0.18%
					TP53 H179R 0.12%
					RAF1 amplification

9	HCV	N/A	N/A	Day 0	TP53 H193R 0.92%	APC N1919K 0.26%	13	6 (A)
						ERBB2 V1128I 8.71%

10	HCV	RB1 loss exons 7–17	Day 0	Day 431		ARID1A Q171H 0.31%	7360	7 (B)
		RB1 loss exons 7–17				BRCA2 F1219L 0.42%

		TERT promoter −124C>T		Day 634	TP53 A138V 0.12%	BRCA1 R866C 0.19%
		TERT promoter −124C>T				BRCA2 F1219L 0.12%

11	Alcohol	N/A	N/A	Day 0	TP53 R273C 12.08%	APC T683I 2.74%	8990	10 (C)
					ERBB2 amplification
					MYC amplification

				Day 133	TP53 R273C 40.57%	APC T683I 10.09%
					ERBB2 amplification
					MYC amplification

12	Metabolic Syndrome	N/A	N/A	Day 0	TP53 S241F 0.13%	ESR1 P592R 0.10%	4	9 (B)

13	Alcohol	N/A	N/A	Day 0	ARID1A Q268* 0.21%	APC S2533F 0.10%	72	7 (B)
						ARID1A E1531K 0.27%
						RAF1 E278K 0.23%
						SMAD4 V354E 1.77%

14	Alcohol	CCND1 amplification	Day 0	Day 34		NFE2L2 F37S 0.48%	75	8 (B)
		CCND1 amplification				FGFR2 G570S 0.12%
		ERRFI1 S302fs*10				CCND1 E135K 0.10%
		VEGFA amplification
		FGF19 amplification

15	HCV	N/A	N/A	Day 0		CDK6 H297Y 0.27%	N/A	N/A
						MYC R98W 0.30%

16	HCV	No alterations	Day 0	Day 876		ARID1A E2078K 0.12%	1.9	7 (B)

17	HCV	CTNNB1 S45P	Day 0	Day 308	CTNNB1 S45P 15.35%	CCND2 D264G 1.26%	5	10 (C)
		GNAS R201C			TP53 H214R 0.29%	NF1 G2499S 0.19%
		TP53 W146fs*2				FGFR2 K539E 0.13%

		IRF2 W46^*		Day 350	CTNNB1 S45P 26.04%	CCND2 D264G 1.58%
		TERT promoter −124C>T			TP53 H214R 0.39%	RET K710N 0.17%

18	HCV	N/A	N/A	Day 0	ERBB2 R143Q 0.12%	CDKN2A S12L 0.38%	1256	8 (B)
					TP53 H178D 2.27%	KIT D975N 0.11%
						NF1 R2179C 0.10%

19	HCV	CDKN2A p16INK4a M52fs*1	Day 0	Day 671	CTNNB1 S45F 2.85%		1899	8 (B)
		p14ARF H66fs*68+
		CTNNB1 S45F
		KEAP1 R260^*
		RBM10 Q518^*
		TERT promoter −124C>T

20	Metabolic Syndrome	N/A	N/A	Day 0	TP53 K139N 0.69%	ATM R337C 0.43%	2134	7 (B)
						JAK3 M576K 0.44%

21	HCV	FBXW7 E113D – subclonal	Day 0	Day 63	PIK3CA H1047L 0.55%	KRAS I24L 2.29%	55	7 (B)
		FBXW7 E113D – subclonal			TP53 R280G 2.90%
		CDKN2A/B loss			TP53 H193R 2.57%
		AXIN1 R395P – subclonal
		TERT promoter −124C>T

22	Metabolic Syndrome	N/A	N/A	Day 0	TP53 C176F 7.95%	MET P4S 6.48%	2	6 (A)

23	HCV	KIT V399I	Day 29	Day 0	ARID1A E1668* 0.53%	ATM N3003S 0.35%	17.2	6 (A)
		ARID1A E1668^*			CTNNB1 S37F 0.75%	BRCA1 N941D 1.35%
		CTNNB1 S37F
		TERT promoter −124C>T

24	HCV	N/A	N/A	Day 0	TP53 R249S 31.96%	FGFR1 E464K 0.20%	571000	11 (C)
					TP53 R196Q 0.19%
					KRAS amplification
					CCNE1 amplification
					CDK4 amplification

25	HCV	N/A	N/A	Day 0	MET I491T 0.14%		2	8 (B)

26	HCV	N/A	N/A	Day 0	AR R608Q 0.68%	KIT D975N 0.27%	3	7 (B)
					CTNNB1 T41A 2.35%	MYC S154L 0.18%
					NFE2L2 E82G 1.91%	NTRK1 E413K 0.15%
					TP53 R248G 2.03%	RB1 M704R 1.69%
						TSC1 E1101K 0.11%

Abbreviations: ctDNA = circulating tumor DNA; HBV = hepatitis B; HCC = hepatocellular carcinoma; HCV = hepatitis C; N/A = not available; VUS = variant of unknown significance

Day 0 represents the original test date.

^**

All patients had genomic testing by Foundation One (http://foundationone.com/), except for patient #16, whose testing was performed by Molecular Health (626 genes)

^***

AFP level closest in date to ctDNA blood draw was chosen