Supplementary Tables: Table S8 Ic50s of DPC4/SMAD4 Isogenic Cells

Supplementary tables:

Table S8 IC50s of DPC4/SMAD4 isogenic cells tested with Cisplatin, Irinotecan and Gemcitabine*

Drug Isogenic cell lines Genotype TGFB pathway IC50 (nM) Fold between P of DPC4 activity means value Cisplatin Pa01C-DPC4-1 + 4.06 1524.00±259.90 1.82 0.040 Pa01C-Control-1 - 0.86 837.70±166.50 Pa01C-DPC4-2 + 3.35 1055.00±294.50 1.23 0.307 Pa01C-Control-2 - 1.24 858.70±150.70 Pa02C-DPC4-1 + 1.68 601.40±47.17 1.15 0.060 Pa02C-Control-1 - 1.11 523.00±29.69 Pa02C-DPC4-2 + 1.46 809.30±55.56 1.27 0.028 Pa02C-Control-2 - 1.12 636.90±75.43 Irinotecan Pa01C-DPC4-1 + 4.06 1491.00±83.81 1.20 0.077 Pa01C-Control-1 - 0.86 1239.00±24.11 Pa01C-DPC4-2 + 3.35 1538.00±131.6 1.70 0.030 Pa01C-Control-2 - 1.24 903.60±54.18 Pa02C-DPC4-1 + 1.68 1787.00±134.30 1.40 0.080 Pa02C-Control-1 - 1.11 1274.00±112.40 Pa02C-DPC4-2 + 1.46 2393.00±98.52 1.37 0.044 Pa02C-Control-2 - 1.12 1745.00±48.01 Gemcitabine Pa01C-DPC4-1 + 4.06 4.27±0.70 0.51 0.058 Pa01C-Control-1 - 0.86 8.42±0.60 Pa01C-DPC4-2 + 3.35 3.70±0.62 0.47 0.033 Pa01C-Control-2 - 1.24 7.85±1.27 Pa02C-DPC4-1 + 1.68 5.75±0.17 0.56 0.055 Pa02C-Control-1 - 1.11 6.77±0.14 Pa02C-DPC4-2 + 1.46 4.73±0.69 0.58 0.186 Pa02C-Control-2 - 1.12 8.14±1.27 * Differences of IC50 value for isogenic pairs were compared with paired t-test analysis.

Table S9 Correlation analysis between IC50s of Cisplatin, Irinotecan and Gemcitabine and TGFB pathway activity of DPC4 isogenic cells *

Drug Correlation r 95% confidence interval P value Cisplatin 0.86 0.39 to 0.97 0.007 Irinotecan 0.07 -0.67 to 0.74 0.067 Gemcitabine -0.81 -0.96 to -0.25 0.015 * Correlations analysis was performed by Spearman method.

Table S10 Genes whose expression levels were correlated with chemosensitivity in pancreatic cancer cell lines *

Drug Gene Correlation r Lower limit Upper limit P value MMC ABL2 0.77 0.49 0.91 0.000 ADAT2 0.72 0.40 0.89 0.000 ADH5 0.76 0.46 0.90 0.000 ANKRD27 0.70 0.37 0.88 0.001 APBB2 0.70 0.36 0.87 0.001 APOBEC3B 0.70 0.35 0.87 0.001

ATAD2 0.81 0.57 0.92 0.000 B3GNT2 0.72 0.40 0.89 0.000 BCAT1 0.85 0.65 0.94 0.000 C4orf32 0.71 0.38 0.88 0.001 C8orf76 0.76 0.47 0.90 0.000 CEBPZ 0.71 0.37 0.88 0.001 CKAP2L 0.76 0.47 0.90 0.000 CLIC4 0.74 0.44 0.90 0.000 CLOCK 0.70 0.37 0.88 0.001 CNOT10 0.72 0.40 0.89 0.000 CTH 0.78 0.50 0.91 0.000 CXorf10 0.72 0.40 0.89 0.000 DAAM1 0.72 0.40 0.89 0.000 DDEF1 0.77 0.48 0.91 0.000 DIAPH2 0.72 0.39 0.88 0.001 DRD1 0.74 0.43 0.89 0.000 EHD4 0.87 0.69 0.95 0.000 FAM49B 0.71 0.38 0.88 0.001 FAM54A 0.72 0.39 0.88 0.001 FAM84B 0.74 0.43 0.89 0.000 FMNL1 0.74 0.43 0.89 0.000 FRMD6 0.88 0.72 0.95 0.000 FUT8 0.73 0.41 0.89 0.000 GPR125 0.74 0.42 0.89 0.000 HMGA1 0.70 0.36 0.87 0.001 HOOK3 0.71 0.37 0.88 0.001 KIAA0196 0.81 0.55 0.92 0.000 KIAA1524 0.70 0.36 0.87 0.001 LARP7 0.82 0.58 0.93 0.000 LIMS1 0.70 0.36 0.88 0.001 LOC100009676 0.87 0.68 0.95 0.000 LOC100128389 0.70 0.36 0.88 0.001 LOC341784 0.74 0.42 0.89 0.000 LOC728931 0.70 0.36 0.88 0.001 LOC730733 0.76 0.47 0.90 0.000 LOXL1 0.77 0.49 0.91 0.000 LRAT 0.76 0.47 0.90 0.000 LRCH3 0.85 0.64 0.94 0.000 LYAR 0.73 0.41 0.89 0.000 MRPL13 0.71 0.38 0.88 0.001 MTERFD1 0.70 0.36 0.87 0.001 MTIF2 0.70 0.35 0.87 0.001 MYH9 0.81 0.56 0.92 0.000 NM_201437.1 0.76 0.46 0.90 0.000 NR1D2 0.75 0.44 0.90 0.000 NRP1 0.74 0.43 0.89 0.000 NSMCE2 0.77 0.49 0.91 0.000 PABPC3 0.73 0.42 0.89 0.000 PDE5A 0.73 0.4 0.89 0.000 PLRG1 0.70 0.37 0.88 0.001

PMAIP1 0.79 0.53 0.92 0.000 RASA1 0.75 0.44 0.9 0.000 RBPJ 0.75 0.45 0.90 0.000 RCC2 0.71 0.38 0.88 0.001 RGNEF 0.78 0.51 0.91 0.000 RNF123 0.72 0.39 0.88 0.001 RNF139 0.83 0.60 0.93 0.000 RPP30 0.78 0.50 0.91 0.000 SCLT1 0.72 0.40 0.89 0.000 SDAD1 0.72 0.39 0.88 0.001 SERPINB5 0.70 0.37 0.88 0.001 SNX14 0.70 0.36 0.88 0.001 SPRED2 0.77 0.49 0.91 0.000 STK17B 0.72 0.39 0.88 0.001 TATDN1 0.75 0.44 0.90 0.000 TES 0.75 0.45 0.90 0.000 THAP1 0.73 0.41 0.89 0.000 TNS4 0.71 0.37 0.88 0.001 TRIB1 0.72 0.39 0.88 0.001 TTK 0.77 0.49 0.91 0.000 UNQ3104 0.77 0.49 0.91 0.000 VEGFC 0.74 0.43 0.89 0.000 WDR67 0.73 0.42 0.89 0.000 ZNF502 0.73 0.41 0.89 0.000 ZNF703 0.77 0.48 0.91 0.000 Triptolide ACSS1 0.78 0.51 0.91 0.000 ADPRHL2 0.74 0.43 0.89 0.000 ALPPL2 0.8 0.54 0.92 0.000 AQP1 0.82 0.58 0.93 0.000 AXIN2 0.71 0.38 0.88 0.001 B4GALT2 0.78 0.51 0.91 0.000 BDH2 0.86 0.66 0.94 0.000 C1orf130 0.74 0.44 0.90 0.000 C1orf212 0.70 0.36 0.87 0.001 C1orf91 0.77 0.49 0.91 0.000 C9orf41 0.75 0.44 0.90 0.000 CCDC109B 0.74 0.43 0.89 0.000 CCNI2 0.69 0.35 0.87 0.001 CLCN1 0.76 0.46 0.90 0.000 CMPK2 0.79 0.53 0.92 0.000 CNFN 0.78 0.50 0.91 0.000 CNN3 0.70 0.36 0.88 0.001 COL7A1 0.72 0.39 0.88 0.001 CPS1 0.77 0.48 0.91 0.000 ETV7 0.79 0.52 0.91 0.000 FAM26A 0.74 0.43 0.89 0.000 FAM46C 0.87 0.69 0.95 0.000 FGFR4 0.74 0.43 0.89 0.000 FLJ12355 0.73 0.41 0.89 0.000 GAB2 0.76 0.47 0.90 0.000

GIPC2 0.79 0.52 0.92 0.000 GJB5 0.88 0.72 0.96 0.000 GMEB2 0.78 0.51 0.91 0.000 GNPTAB 0.77 0.49 0.91 0.000 GPX2 0.73 0.42 0.89 0.000 HECTD3 0.72 0.39 0.88 0.001 HIVEP3 0.79 0.52 0.91 0.000 HOMEZ 0.71 0.38 0.88 0.001 IFI6 0.70 0.36 0.88 0.001 IFITM1 0.70 0.35 0.87 0.001 IFITM3 0.90 0.75 0.96 0.000 IGBP1 0.77 0.49 0.91 0.000 IL2RG 0.77 0.49 0.91 0.000 KIAA1542 0.72 0.39 0.88 0.001 KRT6B 0.72 0.39 0.88 0.001 LDHA 0.78 0.5 0.91 0.000 LDHD 0.72 0.39 0.88 0.001 LGR6 0.89 0.73 0.96 0.000 LOC100128968 0.77 0.48 0.91 0.000 LOC100129792 0.74 0.44 0.90 0.000 LOC130576 0.81 0.56 0.92 0.000 LOC284578 0.81 0.57 0.93 0.000 LOC728392 0.75 0.46 0.90 0.000 LOC728509 0.71 0.38 0.88 0.001 LRIG2 0.76 0.47 0.90 0.000 MAGOH 0.74 0.43 0.89 0.000 MAST2 0.71 0.37 0.88 0.001 MATN4 0.72 0.39 0.88 0.001 MED23 0.72 0.39 0.88 0.001 MFSD4 0.83 0.6 0.93 0.000 MGC12982 0.80 0.55 0.92 0.000 MGC39821 0.81 0.57 0.93 0.000 MMP7 0.80 0.55 0.92 0.000 MOBKL2C 0.83 0.61 0.93 0.000 MYB 0.72 0.39 0.88 0.001 NAB1 0.72 0.40 0.89 0.000 NES 0.75 0.46 0.90 0.000 PANK1 0.79 0.53 0.92 0.000 PBLD 0.71 0.37 0.88 0.001 PDZK1IP1 0.81 0.57 0.92 0.000 PFKFB4 0.90 0.74 0.96 0.000 PIGR 0.80 0.54 0.92 0.000 PKP1 0.90 0.76 0.96 0.000 PLEKHA4 0.74 0.43 0.89 0.000 PNKD 0.69 0.35 0.87 0.001 POU2AF1 0.71 0.38 0.88 0.001 PPAP2A 0.75 0.46 0.90 0.000 Q8N1K6_HUMAN 0.80 0.53 0.92 0.000 RAB6B 0.89 0.73 0.96 0.000 RABAC1 0.80 0.55 0.92 0.000

RERGL 0.77 0.49 0.91 0.000 RHOC 0.81 0.57 0.93 0.000 SERPINA3 0.73 0.41 0.89 0.000 SHISA5 0.73 0.42 0.89 0.000 SIRPA 0.73 0.42 0.89 0.000 SLC19A3 0.83 0.61 0.93 0.000 SLC2A1 0.70 0.36 0.88 0.001 SNIP1 0.81 0.56 0.92 0.000 STX7 0.69 0.35 0.87 0.001 SULT1C2 0.73 0.42 0.89 0.000 SYNGR3 0.84 0.62 0.94 0.000 TESK2 0.74 0.44 0.90 0.000 TUSC1 0.86 0.66 0.94 0.000 UBD 0.84 0.62 0.94 0.000 VDAC3 0.77 0.49 0.91 0.000 WDR44 0.73 0.41 0.89 0.000 WNT11 0.79 0.52 0.91 0.000 ZNF18 0.74 0.43 0.89 0.000 ZNF776 0.73 0.42 0.89 0.000 ZNRD1 0.84 0.62 0.94 0.000 Aretmisinin ABP1 -0.71 -0.88 -0.37 0.001 ATP5G1 -0.74 -0.9 -0.44 0.000 C6orf223 -0.71 -0.88 -0.38 0.001 DCTN2 -0.72 -0.89 -0.40 0.000 DNAJC11 -0.73 -0.89 -0.41 0.000 FAM100A -0.70 -0.88 -0.37 0.001 FAM125B -0.89 -0.96 -0.74 0.000 GCN5L2 -0.70 -0.88 -0.36 0.001 HDDC2 -0.71 -0.88 -0.38 0.001 HDDC3 -0.70 -0.88 -0.36 0.001 LOC100130418 -0.70 -0.87 -0.35 0.001 LOC283270 -0.70 -0.88 -0.37 0.001 LOC93349 -0.73 -0.89 -0.41 0.000 METTL1 -0.77 -0.91 -0.48 0.000 PTMS -0.79 -0.92 -0.53 0.000 PYGB -0.70 -0.87 -0.36 0.001 RAET1G -0.80 -0.92 -0.53 0.000 SLC9A3R1 -0.70 -0.88 -0.37 0.001 STOML1 -0.70 -0.87 -0.35 0.001 SYNE1 -0.75 -0.90 -0.44 0.000 TARBP2 -0.70 -0.88 -0.37 0.001 TIMELESS -0.70 -0.88 -0.36 0.001 TMEM176B -0.71 -0.88 -0.38 0.001 TMEM180 -0.77 -0.91 -0.49 0.000 UCP2 -0.76 -0.90 -0.47 0.000 ZBTB3 -0.70 -0.87 -0.35 0.001 Gemcitabine AADAC 0.75 0.45 0.90 0.000 AARS 0.70 0.36 0.88 0.001 ABCA10 0.74 0.43 0.89 0.000 ABCG2 0.77 0.48 0.91 0.000

ABI3BP 0.70 0.37 0.88 0.001 ACSF3 0.75 0.46 0.90 0.000 ADFP 0.75 0.45 0.90 0.000 AL953854.2 0.89 0.73 0.96 0.000 ALKBH4 0.71 0.38 0.88 0.001 ARHGEF9 0.81 0.57 0.93 0.000 ATP6V1H 0.72 0.40 0.89 0.000 C11orf46 0.77 0.48 0.91 0.000 C11orf61 0.70 0.36 0.87 0.001 C3 0.73 0.41 0.89 0.000 C4B 0.70 0.35 0.87 0.001 CDGAP 0.77 0.48 0.91 0.000 CES3 0.71 0.38 0.88 0.001 CFDP1 0.80 0.55 0.92 0.000 CHAC1 0.72 0.39 0.88 0.001 CNTNAP3 0.83 0.61 0.93 0.000 CNTNAP3B 0.89 0.74 0.96 0.000 COL9A2 0.75 0.44 0.90 0.000 CPM 0.73 0.41 0.89 0.000 CSTA 0.73 0.41 0.89 0.000 ERMP1 0.71 0.38 0.88 0.001 FBXL12 0.80 0.55 0.92 0.000 FEZ2 0.73 0.42 0.89 0.000 FLJ10357 0.70 0.36 0.88 0.001 FLJ33630 0.69 0.35 0.87 0.001 FTO 0.73 0.41 0.89 0.000 FUK 0.87 0.68 0.95 0.000 GLRX 0.75 0.45 0.90 0.000 HMCN2 0.70 0.37 0.88 0.001 HSF4 0.74 0.43 0.89 0.000 ICAM1 0.76 0.47 0.90 0.000 IFI16 0.77 0.48 0.91 0.000 IFNGR1 0.78 0.50 0.91 0.000 IRAK3 0.78 0.50 0.91 0.000 KIAA0515 0.77 0.48 0.91 0.000 KIAA0913 0.76 0.46 0.90 0.000 KIAA1024 0.72 0.39 0.88 0.001 LDB1 0.83 0.60 0.93 0.000 LDLR 0.76 0.47 0.90 0.000 LIMK1 0.76 0.47 0.90 0.000 LINCR 0.73 0.41 0.89 0.000 LMO2 0.76 0.46 0.90 0.000 LOC100132985 0.73 0.41 0.89 0.000 LOC285628 0.77 0.49 0.91 0.000 LSDP5 0.71 0.38 0.88 0.001 LTB4R 0.77 0.48 0.91 0.000 LYPLA3 0.71 0.38 0.88 0.001 MAP3K10 0.73 0.41 0.89 0.000 2-Mar 0.72 0.39 0.88 0.001 MC1R 0.74 0.44 0.90 0.000

MED16 0.71 0.37 0.88 0.001 MLKL 0.70 0.36 0.88 0.001 MMP15 0.72 0.40 0.89 0.001 MOSPD3 0.72 0.39 0.88 0.001 MYO1F 0.73 0.42 0.89 0.000 NEDD9 0.69 0.35 0.87 0.001 NOTCH3 0.70 0.36 0.87 0.001 NTN4 0.71 0.38 0.88 0.001 OCRL 0.77 0.49 0.91 0.000 ORAI2 0.73 0.41 0.89 0.000 OSR1 0.77 0.49 0.91 0.000 PCDHB10 0.79 0.53 0.92 0.000 PFKFB3 0.70 0.37 0.88 0.001 PHF1 0.74 0.43 0.89 0.000 PPP2R5B 0.70 0.36 0.88 0.001 PREB 0.70 0.36 0.87 0.001 RAB24 0.77 0.49 0.91 0.000 RABGAP1 0.74 0.43 0.89 0.000 RIN3 0.69 0.35 0.87 0.001 RNF130 0.76 0.47 0.90 0.000 ROBO3 0.84 0.61 0.93 0.000 SAA4 0.78 0.50 0.91 0.000 SAT1 0.72 0.40 0.89 0.000 SETD1A 0.73 0.42 0.89 0.000 SGSH 0.72 0.40 0.89 0.000 SH2D1B 0.87 0.68 0.95 0.000 SIN3B 0.83 0.6 0.93 0.000 SLC11A2 0.78 0.51 0.91 0.000 SLC35E1 0.70 0.36 0.87 0.001 SMARCAL1 0.76 0.46 0.90 0.000 SNPH 0.75 0.44 0.90 0.000 SPOCD1 0.71 0.38 0.88 0.001 STAT6 0.72 0.39 0.88 0.001 TAOK2 0.77 0.48 0.91 0.000 TBL2 0.70 0.36 0.88 0.001 TBRG1 0.82 0.59 0.93 0.000 TNFAIP2 0.81 0.57 0.93 0.000 TNFRSF9 0.73 0.41 0.89 0.000 TPCN1 0.83 0.60 0.93 0.000 TSC22D3 0.83 0.59 0.93 0.000 VNN2 0.72 0.39 0.88 0.001 WIZ 0.76 0.46 0.90 0.000 WNK4 0.70 0.37 0.88 0.001 ZMYM3 0.71 0.38 0.88 0.001 ZNF280C 0.78 0.50 0.91 0.000 ZNF319 0.75 0.44 0.90 0.000 ZNF616 0.71 0.38 0.88 0.001 Docetaxel AL953854.2 0.71 0.38 0.88 0.001 ALDH1L2 0.72 0.40 0.89 0.000 CNTNAP3B 0.78 0.50 0.91 0.000

FAM50A 0.69 0.35 0.87 0.001 FLNA 0.73 0.41 0.89 0.000 GALNAC4S.6ST 0.72 0.4 0.89 0.000 KIAA0515 0.73 0.42 0.89 0.000 LIMK1 0.71 0.37 0.88 0.001 LOC285628 0.71 0.38 0.88 0.001 MERTK 0.69 0.35 0.87 0.001 NFAT5 0.80 0.54 0.92 0.000 NT5C2 0.71 0.38 0.88 0.001 PALM2 0.72 0.39 0.88 0.001 SLFN5 0.76 0.46 0.90 0.000 ZNF177 0.70 0.36 0.88 0.001 ZNF553 0.73 0.41 0.89 0.000 Irinotecan ANKMY1 0.72 0.39 0.88 0.001 ARPC1B 0.77 0.48 0.91 0.000 C16orf44 0.72 0.4 0.89 0.000 CEBPD 0.80 0.54 0.92 0.000 CTSO 0.78 0.51 0.91 0.000 FAM8A1 0.77 0.48 0.90 0.000 FCGBP 0.77 0.49 0.91 0.000 GABARAPL1 0.75 0.45 0.90 0.000 MAP1LC3B 0.69 0.35 0.87 0.001 NFIL3 0.76 0.47 0.90 0.000 PPIC 0.74 0.44 0.90 0.000 RIOK3 0.70 0.37 0.88 0.001 STARD5 0.70 0.37 0.88 0.001 TXNDC4 0.75 0.44 0.90 0.000 UNC50 0.75 0.46 0.90 0.000 Parp1 APBA2BP -0.71 -0.88 -0.37 0.001 inhibitor CDC37 0.73 0.41 0.89 0.000 KIAA1648 -0.76 -0.90 -0.48 0.000 LRRC23 -0.72 -0.88 -0.39 0.001 MRPL35 -0.71 -0.88 -0.38 0.001 PIM3 -0.70 -0.88 -0.36 0.001 Q8N9D4_HUMAN 0.74 0.44 0.90 0.000 TMEM198 -0.72 -0.88 -0.39 0.001 TSPAN5 0.70 0.37 0.88 0.001 USP5 -0.80 -0.92 -0.53 0.000 Cisplatin ACOT7 0.79 0.53 0.92 0.000 ADIPOR1 0.71 0.39 0.88 0.001 AGPAT1 0.81 0.57 0.93 0.000 AKR1C1 0.83 0.61 0.93 0.000 AKT1S1 0.78 0.51 0.91 0.000 ALDH3A1 0.75 0.46 0.90 0.000 AMDHD2 0.72 0.39 0.88 0.001 ANXA6 0.85 0.63 0.94 0.000 AP1M1 0.75 0.45 0.90 0.000 AP1S1 0.69 0.35 0.87 0.001 ARHGAP22 0.86 0.67 0.95 0.000

ARHGEF10L 0.72 0.40 0.89 0.000 ARS2 0.72 0.39 0.88 0.001 ASNA1 0.73 0.42 0.89 0.000 ATP6V0C 0.79 0.52 0.91 0.000 ATP6V0E1 0.85 0.65 0.94 0.000 ATP8B2 0.78 0.50 0.91 0.000 BRD2 0.73 0.42 0.89 0.000 C10orf35 0.75 0.46 0.90 0.000 C14orf149 0.73 0.41 0.89 0.000 C14orf172 0.74 0.42 0.89 0.000 C16orf24 0.73 0.42 0.89 0.000 C17orf67 0.77 0.49 0.91 0.000 C19orf60 0.74 0.42 0.89 0.000 C1orf35 0.81 0.57 0.93 0.000 C1QTNF1 0.83 0.61 0.93 0.000 C1R 0.83 0.59 0.93 0.000 C4B 0.73 0.42 0.89 0.000 C4BPB 0.82 0.59 0.93 0.000 CAD 0.75 0.45 0.90 0.000 CALU 0.70 0.36 0.87 0.001 CCK 0.86 0.67 0.95 0.000 CCND3 0.72 0.40 0.89 0.000 CD14 0.87 0.69 0.95 0.000 CD44 0.72 0.40 0.89 0.000 CD74 0.69 0.35 0.87 0.001 CD99L2 0.77 0.48 0.91 0.000 CDC42BPA 0.75 0.45 0.90 0.000 CDGAP 0.73 0.41 0.89 0.000 CFDP1 0.70 0.36 0.88 0.001 CHCHD2 0.76 0.47 0.90 0.000 CHST10 0.83 0.60 0.93 0.000 CLCN7 0.81 0.56 0.92 0.000 CLDN11 0.83 0.60 0.93 0.000 CNPY4 0.75 0.44 0.90 0.000 COL13A1 0.88 0.71 0.95 0.000 COPZ2 0.86 0.66 0.94 0.000 COQ6 0.75 0.45 0.90 0.000 CRAMP1L 0.70 0.35 0.87 0.001 CRIP2 0.71 0.38 0.88 0.001 CSAD 0.71 0.37 0.88 0.001 CST1 0.85 0.64 0.94 0.000 CST2 0.87 0.68 0.95 0.000 CST4 0.85 0.65 0.94 0.000 CTGLF1 0.74 0.42 0.89 0.000 CTSZ 0.71 0.37 0.88 0.001 DCTN3 0.73 0.41 0.89 0.000 DEGS1 0.90 0.75 0.96 0.000 DRAP1 0.71 0.38 0.88 0.001 DUOXA2 0.79 0.52 0.92 0.000 ECE1 0.75 0.45 0.90 0.000

EFEMP2 0.86 0.67 0.95 0.000 EHD1 0.73 0.41 0.89 0.000 EMP3 0.79 0.52 0.91 0.000 ENG 0.81 0.56 0.92 0.000 EPHA2 0.78 0.51 0.91 0.000 EPHX1 0.74 0.44 0.90 0.000 ETV5 0.76 0.47 0.90 0.000 F10 0.77 0.49 0.91 0.000 FAIM3 0.77 0.48 0.91 0.000 FBLN5 0.73 0.41 0.89 0.000 FEZ1 0.83 0.61 0.93 0.000 FLJ10404 0.71 0.37 0.88 0.001 FLJ20489 0.85 0.65 0.94 0.000 FLJ42709 0.72 0.40 0.88 0.001 FLYWCH1 0.81 0.56 0.92 0.000 FLYWCH2 0.70 0.36 0.88 0.001 FTL 0.69 0.35 0.87 0.001 G6PD 0.81 0.57 0.93 0.000 GAMT 0.81 0.57 0.92 0.000 GDPD5 0.77 0.48 0.91 0.000 GEFT 0.76 0.46 0.90 0.000 GJC2 0.78 0.5 0.91 0.000 GNAZ 0.72 0.40 0.89 0.001 GNS 0.76 0.47 0.90 0.000 GPSM3 0.79 0.52 0.92 0.000 GRN 0.71 0.37 0.88 0.001 HAGH 0.79 0.52 0.91 0.000 HEXIM2 0.69 0.35 0.87 0.001 HLA.C 0.72 0.39 0.88 0.001 HLA.DMA 0.77 0.48 0.91 0.000 HLA.DMB 0.88 0.71 0.95 0.000 HLA.DPA1 0.71 0.38 0.88 0.001 HLA.DRA 0.81 0.57 0.93 0.000 HLA.DRB5 0.88 0.72 0.96 0.000 HLX 0.86 0.67 0.95 0.000 HSD11B1L 0.82 0.57 0.93 0.000 HSP90AB1 0.75 0.44 0.90 0.000 HSPG2 0.84 0.63 0.94 0.000 IGF2BP1 0.75 0.44 0.90 0.000 ISL1 0.81 0.56 0.92 0.000 KATNAL1 0.74 0.42 0.89 0.000 KCND1 0.85 0.65 0.94 0.000 KIAA0040 0.86 0.67 0.95 0.000 KIAA0427 0.91 0.77 0.96 0.000 KIAA0513 0.85 0.64 0.94 0.000 KIAA0586 0.76 0.47 0.9 0.000 KIAA1949 0.81 0.56 0.92 0.000 KIF3C 0.73 0.42 0.89 0.000 KIFC3 0.76 0.46 0.90 0.000 KRBA1 0.70 0.35 0.87 0.001

LMO2 0.76 0.46 0.90 0.000 LOC100128680 0.85 0.65 0.94 0.000 LOC100130776 0.85 0.65 0.94 0.000 LOC100131017 0.73 0.42 0.89 0.000 LOC100132014 0.87 0.7 0.95 0.000 LOC114227 0.73 0.42 0.89 0.000 LOC130355 0.73 0.42 0.89 0.000 LOC153577 0.84 0.61 0.93 0.000 LOC285831 0.83 0.59 0.93 0.000 LOC349114 0.71 0.37 0.88 0.001 LOC388588 0.75 0.45 0.90 0.000 LOC730098 0.75 0.44 0.90 0.000 LOC90110 0.77 0.49 0.91 0.000 LRG1 0.75 0.45 0.9 0.000 LRP1 0.81 0.56 0.92 0.000 LRRC33 0.89 0.73 0.96 0.000 LTBP2 0.75 0.45 0.90 0.000 LY96 0.75 0.44 0.90 0.000 MAP3K12 0.81 0.57 0.93 0.000 MAP4K2 0.86 0.67 0.94 0.000 MAPK11 0.76 0.46 0.9 0.000 MBNL1 0.79 0.52 0.91 0.000 MFSD7 0.73 0.42 0.89 0.000 MORC4 0.75 0.46 0.90 0.000 MPG 0.75 0.46 0.90 0.000 MRPL28 0.77 0.48 0.91 0.000 MT1L 0.76 0.46 0.90 0.000 MYL6 0.71 0.37 0.88 0.001 MYLK2 0.78 0.51 0.91 0.000 NADK 0.78 0.51 0.91 0.000 NDUFA11 0.72 0.40 0.89 0.000 NDUFS7 0.70 0.36 0.87 0.001 NIT2 0.82 0.58 0.93 0.000 NOL7 0.81 0.57 0.93 0.000 NPAS1 0.84 0.62 0.94 0.000 NPAS2 0.75 0.46 0.90 0.000 NTSR1 0.88 0.71 0.95 0.000 NUBP1 0.69 0.35 0.87 0.001 NUDC 0.77 0.49 0.91 0.000 NUMA1 0.74 0.43 0.89 0.000 OGDH 0.72 0.40 0.89 0.000 OSGIN1 0.81 0.57 0.93 0.000 OSTM1 0.79 0.52 0.91 0.000 P2RX6 0.77 0.49 0.91 0.000 P76 0.80 0.54 0.92 0.000 PARC 0.82 0.58 0.93 0.000 PAR.SN 0.81 0.56 0.92 0.000 PCDHGB6 0.82 0.58 0.93 0.000 PCGF2 0.79 0.53 0.92 0.000 PCYT1A 0.70 0.37 0.88 0.001

PDX1 0.81 0.57 0.93 0.000 PHF1 0.73 0.41 0.89 0.000 PHF15 0.80 0.54 0.92 0.000 PI3 0.85 0.65 0.94 0.000 PIGO 0.86 0.68 0.95 0.000 PKM2 0.70 0.35 0.87 0.001 PLEKHG4 0.86 0.67 0.94 0.000 PLEKHM1 0.80 0.55 0.92 0.000 PLXND1 0.73 0.41 0.89 0.000 PNMT 0.80 0.55 0.92 0.000 PRICKLE4 0.80 0.54 0.92 0.000 PRKACA 0.70 0.36 0.87 0.001 PSMB6 0.72 0.40 0.89 0.001 PTPRS 0.71 0.38 0.88 0.001 PTX3 0.75 0.45 0.90 0.000 RAPGEF3 0.71 0.38 0.88 0.001 RARA 0.76 0.47 0.90 0.000 RBP4 0.77 0.49 0.91 0.000 REEP5 0.70 0.36 0.87 0.001 RHOT2 0.80 0.55 0.92 0.000 RNPEP 0.72 0.40 0.89 0.000 ROGDI 0.74 0.44 0.90 0.000 RUSC2 0.77 0.48 0.90 0.000 SAFB 0.72 0.39 0.88 0.001 SCXB 0.78 0.51 0.91 0.000 SEMA4B 0.74 0.42 0.89 0.000 SEMA6B 0.87 0.70 0.95 0.000 SERHL2 0.79 0.52 0.91 0.000 SERPINA5 0.79 0.53 0.92 0.000 SFXN5 0.80 0.54 0.92 0.000 SH3TC1 0.82 0.58 0.93 0.000 SHISA4 0.88 0.71 0.95 0.000 SIGLEC15 0.76 0.47 0.90 0.000 SIPA1 0.79 0.51 0.91 0.000 SLC13A3 0.79 0.52 0.91 0.000 SLC14A1 0.71 0.37 0.88 0.001 SLC25A29 0.74 0.43 0.89 0.000 SLC25A35 0.71 0.37 0.88 0.001 SLC25A44 0.72 0.40 0.88 0.001 SLC35B1 0.77 0.49 0.91 0.000 SLC45A1 0.77 0.49 0.91 0.000 SLC4A2 0.80 0.55 0.92 0.000 SLC9A5 0.82 0.59 0.93 0.000 SMARCD3 0.87 0.68 0.95 0.000 SNX15 0.72 0.39 0.88 0.001 SOD1 0.76 0.46 0.90 0.000 SPEG 0.87 0.69 0.95 0.000 ST3GAL2 0.71 0.38 0.88 0.001 STK17A 0.79 0.52 0.91 0.000 STOML2 0.79 0.53 0.92 0.000

STX10 0.71 0.38 0.88 0.001 SUFU 0.80 0.54 0.92 0.000 TBC1D17 0.72 0.39 0.88 0.001 TBXAS1 0.83 0.61 0.93 0.000 TCEB2 0.75 0.46 0.90 0.000 TEAD2 0.75 0.44 0.90 0.000 TEGT 0.70 0.36 0.88 0.001 TFPI 0.74 0.43 0.89 0.000 TGFB1I1 0.77 0.49 0.91 0.000 THSD4 0.74 0.43 0.89 0.000 TM4SF18 0.79 0.52 0.91 0.000 TM7SF3 0.76 0.46 0.90 0.000 TMEM120A 0.73 0.41 0.89 0.000 TMEM150 0.77 0.49 0.91 0.000 TMEM157 0.75 0.45 0.90 0.000 TNFRSF11A 0.79 0.52 0.92 0.000 TNFRSF18 0.77 0.48 0.91 0.000 TNFRSF9 0.77 0.48 0.91 0.000 TNKS1BP1 0.76 0.46 0.90 0.000 TSC22D4 0.72 0.40 0.89 0.000 TSKU 0.70 0.37 0.88 0.001 TSPAN4 0.76 0.46 0.90 0.000 UAP1L1 0.76 0.47 0.90 0.000 USP12 0.70 0.36 0.88 0.001 VAT1 0.75 0.45 0.90 0.000 VIM 0.75 0.45 0.90 0.000 VNN2 0.71 0.38 0.88 0.001 WDR3 0.82 0.58 0.93 0.000 WDR81 0.74 0.43 0.89 0.000 ZC3H11A 0.72 0.40 0.89 0.000 ZNF467 0.85 0.65 0.94 0.000 * Correlations analysis was performed by Spearman method.

Table S11 Combination indices (CI) for csplatin+irinotecan combination in DPC4 isogenic cell lines*

cell line Combo constant ratio time schedule CI (ID50) CI (ID75) Pa01C-DPC4-1 csplatin+irinotecan 1:1 simutaneously 0.66 1.04 Pa01C-Control-1 cisplatin+irinotecan 1:1 simutaneously 1.31 1.73 Pa01C-DPC4-2 cisplatin+irinotecan 1:1 simutaneously 0.73 0.93 Pa01C-Control-2 cisplatin+irinotecan 1:1 simutaneously 4.38 1.91 * CI: synergism if <1.0, antagonism if >1.0 and additivity if 1.0.

Table S12 IC50s of TP53 isogenic colon cancer cell lines tested with Parp1 inhibitor and Triptolide*

Drug Isogenic cell line Genotype of IC50(nM) P Fold between TP53 value means Parp1 inhibitor hct116-2 -/- 990.60±113.50 0.148 1.37 hct116-8 +/+ 724.90±40.76 rko-249 -/- 1843.00±244.50 0.107 1.45

rko-205 +/+ 1268.00±22.29 sw48-213 -/- 4013.00±208.20 0.001 1.93 sw48-297 +/+ 2075.00±1760 Triptolide hct116-2 -/- 1.00±0.04 0.018 0.73 hct116-8 +/+ 1.37±0.05 rko-249 -/- 0.38±0.02 0.001 0.38 rko-205 +/+ 1.01±0.03 sw48-213 -/- 1.30±0.07 0.010 0.69 sw48-297 +/+ 1.88±0.07 * Differences of IC50 value for isogenic pairs were compared with paired t- test analysis.

Table S13 Comparisons of gene mutation statuses of cell lines having IC50<200nM with those having IC50>10000nM for Parp1 inhibitor*

Amino IC50 of SMAD SMAD TP53 P16. P16. DPC4. DPC4. TGFβR2. Nucleotide acid Hot parp1 Sample Path. Path. Mutation del md del md md (genomic) (protei spot inhibitor del md Type n) 21.67 Pa01C wt wt del del wt del del Missense g.chr17:75191 p.T155 no 92A>C P (homozygous) 185.1 Pa03C wt wt wt wt wt wt wt Missense g.chr17:75147 p.L344 no 21T>C P (homozygous) 91.85 Pa221C wt wt wt mut wt wt mut INDEL g.chr17:75175 fs / 88dupT (homozygous) 138.8 Pa104C wt mut del del wt del del Missense g.chr17:75182 p.G245 yes 73G>A S (homozygous) 105.8 Pa11C del del wt wt wt wt wt Missense g.chr17:75189 p.V217 no 24T>G G (homozygous) Percentage / 0.2 0.4 0.4 0.6 0 0.4 0.6 / / / / >10000 Pa14C del del wt mut wt wt mut del / / / >10000 Pa16C wt wt wt wt mut wt mut Missense g.chr17:75182 p.I255 yes 42T>A N (homozygous) >10000 Pa20C wt mut wt mut wt wt mut Missense g.chr17:75189 p.D208 no 51A>T V (homozygous) >10000 Pa222C wt wt wt wt wt wt wt Missense g.chr17:75147 p.M340 no 34A>G V (homozygous) >10000 Pa34C del del del del wt del del Missense g.chr17:75183 p.Y234 no 05A>G C (homozygous) >10000 Pa02C del del del del wt del del Missense g.chr17:75182 p.L257 no 36T>C P

(homozygous) >10000 Pa08C del del wt mut wt wt mut INDEL g.chr17:75189 fs / 72delT (homozygous) Percentage / 0.57 0.71 0.29 0.71 0.14 0.29 0.86 / / / / * “wt” indicates a wildtype; “mut” indicate a mutation; “del” indicates a deletion; “md” indicates either a mutation or deletion. ”/” indicates there is no relevant item.

Table S14 Genes with significantly different gene expression in cell cycle and DNA damage pathway and other DNA damage repair genes without significant difference between TP53 defective PC cell lines having IC50<200nM and those having IC50>10000nM for Parp1 inhibitor*

Gene Median of SAGE Median of SAGE P Fold between means Fold between medians expression level in expression level in value (sensitivity/resistant) (resistant /sensitivity) sensitive cancer cells resistant cancer cells IC50<200nM IC50>10000nM ERCC3 115 57.12 0.048 2.01 0.50 FOXO1 7.76 10.85 0.048 0.72 1.39 MUTYH 149.7 40.11 0.024 3.73 0.27 PARP6 4.18 95.84 0.024 0.04 25.00 PLK2 8.8 5.91 0.024 1.49 0.67 ALB 15.13 33.21 0.024 0.46 2.19 USP10 40.24 17.67 0.048 2.28 0.44 BRCA1 28.71 23.51 0.768 1.22 0.82 BRCA2 0.13 0.62 0.468 0.20 4.92 ERCC1 19.10 32.29 0.499 0.59 1.69 ERCC2 22.75 16.26 0.457 1.40 0.71 ERCC4 3.45 3.24 0.856 1.07 0.94 ERCC5 18.85 25.47 0.612 0.74 1.35 ERCC6 8.93 5.06 0.254 1.77 0.57 FANCA 22.58 27.46 0.684 0.82 1.22 FANCB 5.84 4.28 0.692 1.36 0.73 FANCC 6.00 6.06 0.984 0.99 1.01 FANCD2 12.12 12.64 0.923 0.96 1.04 FANCE 7.35 9.36 0.674 0.79 1.27 FANCG 15.81 23.58 0.353 0.67 1.49 FANCI 56.63 70.10 0.582 0.81 1.24 FANCL 20.93 12.19 0.208 1.72 0.58 FANCM 4.05 4.86 0.725 0.83 1.20 PARP1 32.84 61.95 0.280 0.53 1.89 PARP10 7.79 7.28 0.801 1.07 0.94 PARP11 116.74 128.18 0.869 0.91 1.10 PARP12 41.79 62.93 0.462 0.66 1.51 PARP14 6.36 5.70 0.892 1.12 0.90 PARP15 8.36 7.77 0.836 1.08 0.93 PARP16 20.74 12.58 0.309 1.65 0.61 PARP2 20.99 6.31 0.332 3.33 0.30 PARP3 117.93 64.80 0.104 1.82 0.55 PARP4 10.04 17.83 0.215 0.56 1.78 PARP8 68.15 37.20 0.288 1.83 0.55

PARP9 4.89 5.14 0.885 0.95 1.05 RAD18 223.25 170.81 0.413 1.31 0.77 RAD21 113.78 128.31 0.835 0.89 1.13 RAD23A 174.40 176.91 0.971 0.99 1.01 RAD23B 40.27 22.98 0.195 1.75 0.57 RAD50 14.05 24.64 0.248 0.57 1.75 RAD51 26.30 23.55 0.778 1.12 0.90 RAD52 15.49 25.52 0.317 0.61 1.65 RAD54B 8.46 7.82 0.892 1.08 0.92 XRCC1 20.59 29.37 0.580 0.70 1.43 XRCC2 9.71 16.49 0.142 0.59 1.70 XRCC3 16.17 9.47 0.328 1.71 0.59 XRCC4 354.47 219.12 0.156 1.62 0.62 XRCC5 293.78 317.74 0.798 0.92 1.08 XRCC6 6.42 5.78 0.819 1.11 0.90 PALB2 17.76 45.90 0.148 0.39 2.58 TP53 12.58 14.68 0.779 0.86 1.17 * Wilcoxon rank sum tests were used to compare differences in median of SAGE expression level by drug response status. Genes listed above the line were selected with statistical significance. Those below the line were involved in double strand break or other DNA repair systems.

Table S15 P16/CDKN2A deleted PC cells rank ordered by their sensitivity to gemcitabine and MMC investigated for association with CDKN2B, DMRTA1, MTAP and TUSC1 in pancreatic cancer cells*

Drug Cell lines IC50 (nM) P16/CDKN2A CDKN2B DMRTA1 MTAP TUSC1 gemcitabine Pa11C 1.13 del del wt wt del Pa37C 1.82 del del wt wt del Pa21C 2.22 del del wt del wt Pa18C 3.39 del del wt wt wt Pa14C 4.43 del del wt wt wt Pa07C 4.61 del wt wt wt wt Pa34C 7.50 del del del del wt Pa04C 7.74 del wt wt del wt Pa02C 12.43 del wt wt wt wt Pa43C 28.30 del del wt del wt Pa08C 47.86 del del del del del Pa09C 63.88 del del del wt del MMC Pa43C 3.16 del del wt del wt Pa21C 4.89 del del wt del wt Pa11C 5.50 del del wt wt del Pa04C 6.34 del wt wt del wt Pa37C 12.13 del del wt wt del Pa34C 19.00 del del del del wt Pa09C 23.85 del del del wt del Pa14C 25.15 del del wt wt wt

Pa08C 26.48 del del del del del Pa02C 54.38 del wt wt wt wt Pa18C 56.66 del del wt wt wt Pa07C 103.00 del wt wt wt wt * Cell lines were ordered according to increasing IC50 for gemcitabine and MMC.“wt” indicates a wildtype; “del” indicates a deletion.