Supplemental Figure 1 A AICDA APOBEC1 APOBEC2 APOBEC3A APOBEC3B 1.2 ● * ● ● ● ● ● 6 ● ● 1.0 ● ● 3 ● ● 1.5 ● ● 3 5 ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● 0.8 ● ● ● ● ● ● 4 ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 2 ● ● ● ● ● ● ● ● ●● 1.0 ● ● ● ● ● ● 2 ● ● ● ● ● ● ● ● ● ● ● ● ● 0.6 ● ●● ● ●● ● ●● ● ●● ● ● ● 3 ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ●● ●● ● ● ● ● ● Log2 (TPM+1) ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● 0.4 ●● ● 2 ●●● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● 1 ● ● ●● ● ● ● 0.5 ● ● ●● ● 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ●● ●●● ● ● ● ●● ● ● ● ● ● 1 ● ● ● ● ●● ● 0.2 ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ●● ● ●●● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ●● ●● ●●●● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ●● ● ● ● ● ● ● ●●●● ● ● ●● ● ● ● ● ●●● ● ● ● ● ● ●● ●●● ● ● ● ● ●● ●●● ●●● ● ● ● ● ● ●● ● ● ●● ● ●● ● ●●●●● ●● ●● ● ● ● ●●● ●●●●● ● ● ● ● ●● ● ● ● ●● ●●●● ●● ● ●●● ● ●●● ● ● ● ● ●●●●● ● ● ● ● ●● ●● ● ●● ● ● ● ● ●●● ●● ●●● ●● ●● ● ● ● ●●●●●●●● ● ● ●● ● ●●●●● ●● ● ●●●● ●●● ● ● ●● ● ● ●● ● ● ●● ●● ● ● ● ● ● ● ●● ● ●● ●●●●● ● ● ● ● ● ●● ● ● ●●●● ●● ● ● ● ● ●● ●●●● ●● ● ●● ●●●●● ● ●● ●● ● ●● ● ● ●●●● ●●●●●● ● ● ●● ● ● ● ● ● ● ●●●● ●●●●● ● ● ● ●●●● ● ●●● ● ●● ●● ● ●●●●●●● ● ● ● ●●●●●●● ●● ●●● ● ●●● ● ● ● ● ●●●●●●● ● ●● ● ● ● ● ●● ●●●●●● ●●●●●●●●●● ●●●● ● ● ●● ● ●● ● ● ● ● ● ●● ● ● ● ●● ● ●● ●●●●● ●●● ●● ● ● ●●●● ●● ● ● ●●●●●●●● ● ● ●●●● ●●●●● ●●● ● ●● ● ● ●● ● ● ● ●●●●●●●●●●●●●●●●●●●●● ●● ● ● ● ●●●●● ●●●●● ● ●● ● ● ● ●●● ● ●●● ●●● ●●● ●● ● ● ● ● ●● ●●●●●●● ●●●●●● ●●●●● ●●●●●●● ●●● ●●●● ●●●●● ● ●●● ● ● ● ● ●●●●●●●●●●●●●●● ●●●●● ● ●●● ● ●●●●●●●● ●●●●● ●●● ●● ● ●●●● ● ●●● ● ●● ● ●●●●●● ● ●●●●●● ●●●●●●●●●●●●●●● ●●●●● ●●●●● ● ●● ● ● ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ● ●●●● ●●● ●●● ● ●●●● ●● ●●●●●●● ● ●● ● ●● ●●● ●●● ● ● ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ●●●●● ●●●●●●●●●● ●●●●●●●●● ●●●●●●●●●●●●●●●●●● ●● ● 0.0 ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● 0.0 ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● 0 0 0 LIHC LIHC LIHC LIHC LIHC (num(T)=369; num(N)=160)(num(T)=369; num(N)=160) (num(T)=369; num(N)=160) (num(T)=369; num(N)=160)(num(T)=369; num(N)=160) APOBEC3C APOBEC3D APOBEC3F APOBEC3G APOBEC3H 4 4 3.0 ● ● ● ● ● 6 ● ● 6 ● ● ● ● ● ● ● ● 2.5 ● 5 ● ● 5 ● ● 3 ● 3 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 2.0 ● ● ● ● ● ● ● ● ● ● 4 4 ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 2 2 ● ● ● ● ● ● ● ● ●● ● ●● ●● ● ● ● ● ● ● ● ● ● ● 1.5 ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● 3 ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● 3 ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ●●● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ● ●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● Log2 (TPM+1) ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ● ●● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● 1.0 ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● 2 ● ●●● ●● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ●● ● ●●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ● ●●● ● ● ● ●● ● ● ● ●● ● ● ● ●● ● ●● ● ●● ● ● ● ● ● ● ● ●● ● ● ●● ●● ● ●● ● ● 2 ●● ● ● ●● ● ●●● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ●● ●● ● ●● ● ● ● ● ● ● ● ● ● ●● ●● ● ●●● ● ● ●● ● ●● ●● ●● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ●● ●● ● ● ● ●● ● ● ● ●●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ●●● ●● ● ●● ● ● ● ● ● ● ●● ●● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● 1 ●● ● ●● ● 1 ● ● ●● ● ● ● ● ● ● ●●●●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ●● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ●●● ● ●● ●● ● ●● ● ● ●● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ●● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●●● ● ● ●●● ●● ● ● ● ● ● ● ● ● ●● ●●●●● ● ● ● ● ●● ● ● ●● ● ● ● ●● ● ●● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●●● ● ● ●● ● ●●● ● ● ●● ●●●●●● ● ●● ● ●●● ●● ● ● ●● ● ●●● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ●● ●● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ●●● ●●●● ● ● ● ● ● ● ● ● ● ● ●● ●●● ● ● ● ● ●●●●● ● ●● ● ● ●●● ● ● ●● ● ●● ● ● ● ● ●● ●● ● ● ● ●●●● ● ●● ●● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ●● ● ●●● ● ● ● ● ●● ● ● ● ● ●● ● ● ●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●●●● ● ● ● ● ● ● ●● ●●● ●●● ● ● ● ● ● ●●● ● ●● ● ● ●● ● ●●● ● ● ● ●● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● 0.5 ●● ● ● ● ●● ●● ● ●● ● ●● ● ● ●● ● ● ● ● ●● ● ●●● ●● ● ●● ● ●● ● ● ●● ● ● ● ●● ●●● ●● ● ●●● ●● ● ●●●●●●● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● 1 ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●●● ● ●● ● ●● ● ● ● ● ● ●● ● ●● ● ● ●● ● ● ●● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ●● ● ●● ●● ● ● ● ● ●● ● ● ●● ●● ● ● ● ●● ● ● ● ●● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ●● ● ● ●● ● ● ● ● ● ●●● ●●● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ●●● ● ● ● ● ● ●● ●● ● ● ● ●● ● ● ●● ● ● ●● ● ●●●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ●● ●● ● ● ● ● ●● ● ● ●●● ● ● ● ● ●● ●● ● ●●● ● ●● ● ● ● ● ●● ● ● ● ● ● ● 1 ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ●●● ● ● ● ● ● ● ●● ● ●● ●●● ● ● ● ● ● ● ● ● ● ●● ●●● ●●● ● ● ● ● ● ● ●●● ● ● ● ●● ● ● ● ● ● ●● ●● ● ● ● ● ● ●● ● ● ●● ●● ● ●● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ●● ● ● ●● ● ● ●● ●● ● ● ● ● ●●●●●●● ●● ●● ●● ● ● ●●●●●●●●●● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ●● ●● ●● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ●●●● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ●● ● ●●● ● ● ● ● ● ● ● ● ● ● ●● ●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ●● ● ●● ● ● ●●● ●● ● ●● ● ● ● ●● ● ● ● ● ● ●● ● ● ●● ●● ●●● ● ●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ●● ●● ● ● ●●● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ●● ● ● ● ● ●● ● ● ● ●●● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ●●● ● ●●●● ●● ● ● ●●● ● ●● ● ● ● ●●● ● ● ●● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0 0 0 ● 0.0 ●● ●●●●●● ● ●●●● LIHC LIHC LIHC LIHC LIHC (num(T)=369; num(N)=160) (num(T)=369; num(N)=160) (num(T)=369; num(N)=160) (num(T)=369; num(N)=160) (num(T)=369; num(N)=160) B GSE45436 Normal Tumor *** Log2 expression AICDA APOBEC1 APOBEC2 A3A A3B A3C A3D A3F A3G A3H C 40 Tumor * Normal s to Actin 30 l eve ion l 20 ess r p ex 10 ve i t a l e R 0 APOBEC3B APOBEC3C APOBEC3D APOBEC3F APOBEC3G APOBEC3H Supplemental Figure 2 A B Overall Survival Disease Free Survival Overall Survival Disease Free Survival Low APOBEC3A TPM Low APOBEC3A TPM Low APOBEC3B TPM 1.0 1.0 1.0 Low APOBEC3B TPM High APOBEC3A TPM High APOBEC3A TPM 1.0 High APOBEC3B TPM High APOBEC3B TPM Logrank p=0.8 al Logrank p=0.078 Logrank p=0.03 al al al v Logrank p=0.037 v HR(high)=0.95 HR(high)=0.76 v HR(high)=1.5 v 0.8 0.8 0.8 vi HR(high)=1.4 vi p(HR)=0.8 vi p(HR)=0.081 p(HR)=0.031 0.8 r vi r r p(HR)=0.038 n(high)=177 n(high)=177 n(high)=181 r n(low)=175 n(low)=175 n(low)=181 n(high)=181 0.6 n(low)=181 0.6 0.6 0.6 0.4 0.4 0.4 ercent su 0.4 ercent su ercent su ercent su P P P P 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120 Months Months Months Months C D Overall Survival Disease Free Survival Overall Survival Disease Free Survival Low APOBEC3C TPM Low APOBEC3D TPM 1.0 Low APOBEC3C TPM 1.0 High APOBEC3C TPM 1.0 Low APOBEC3D TPM Logrank p=0.88 High APOBEC3C TPM High APOBEC3D TPM 1.0 High APOBEC3D TPM al al Logrank p=0.37 al Logrank p=1 al Logrank p=0.22 HR(high)=1 v v v HR(high)=0.87 HR(high)=1 v 0.8 0.8 p(HR)=0.87 0.8 HR(high)=0.83 vi vi vi 0.8 p(HR)=0.36 p(HR)=1 vi r r r n(high)=181 n(high)=181 n(high)=181 r p(HR)=0.22 n(low)=181 n(low)=181 n(low)=181 n(high)=181 0.6 0.6 0.6 n(low)=181 0.6 0.4 0.4 0.4 0.4 ercent su ercent su ercent su ercent su P P P P 0.2 0.2 0.2 0.2 0.0 0.0 0.0 0.0 0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120 Months Months E F Months Months Overall Survival Disease Free Survival