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1 Supplemental Table 1. Antibodies used for RPPA analysis. Label Protein Phosphorylation Site Company Cat # Used on MDA_CLSS Used on MDA_Pilot 4EBP1 4EBP1 Cell Signaling 9452 No 4EBP1.pS65 4EBP1 S65 Cell Signaling 9456 No 4EBP1.pT37.T46 4EBP1 T37 T46 Cell Signaling 9459 No ACC.pS79 Acetyl CoA S79 Cell Signaling 3661 No ACC1 Acetyl CoA Epitomics No AIB.1 Amplified in Breast Cancer BD Pharmingen No AKT AKT Cell Signaling 9272 AKT.pS473 AKT S473 Cell Signaling 9271 AKT.pT308 AKT T308 Cell Signaling 9275 AMPK AMPK Cell Signaling 2532 No AMPK.pT172 AMPK T172 Cell Signaling 2535 No BAD.pS112 BAD S112 Cell Signaling 9296 No BAX BAX Cell Signaling 2772 BCL2 BCL2 Dako M0887 Bim BIM Epitomics No BRCA1 BRCA1 Upstate No Caspase7.C CASPASE 7 Cell Signaling 9491 No CAV1 CAVEOLIN 1 Cell Signaling 3238 No CCNB1 CYCLIN B1 Epitomics 1495 No CCND1 CYCLIN D1 Santa Cruz 718 CCNE1 CYCLIN E1 Santa Cruz 247 No CD31 CD31 Dako M0823 No CDH1 E-CADHERIN Cell Signaling 4065 CDH2 N-CADHERIN Cell Signaling 4061 No CDK4 CDK4 Cell Signaling 2906 No c-jun C-JUN Cell Signaling 9165 No c-kit C-KIT Epitomics No c-myc C-MYC Cell Signaling 9402 c-myc.pt58.s62 C-MYC T58 S62 Cell Signaling 9401 No

2 COX2 COX2 Epitomics No c-raf C-RAF Upstate No CTNNB1 β-catenin Cell Signaling 9562 EGFR EGFR Santa Cruz 3 eif4e eif4e Cell Signaling 9741 No ER.a.pS167 ESTROGEN RECEPTOR S167 Cell Signaling 2514 No ERa.pS118 ESTROGEN RECEPTOR S118 Epitomics No ESR1 ESTROGEN RECEPTOR Neomarkers SP1 FOXO3A FOXO3A Cell Signaling 2514 No FOXO3A.pS318.S3 21 FOXO3A S318 S321 Cell Signaling 9465 No FRAP1 mtor Cell Signaling 2983 GSK3α&β GSK3α&β Santa Cruz 7291 GSK3α&β.pS21.S9 GSK3α&β S21 S9 Cell Signaling 9331 HER2 HER2 Cell Signaling 2242 No HER2.pY1248 HER2 Y1248 Upstate No HER3 HER3 Neomarkers MS201 hnrnp.a1 hnrnp A1 Provided by Dr. Robert Bast No hnrnp.a2.b1 hnrnp A2&B1 Provided by Dr. Robert Bast No IGFBP2 IGFBP2 Cell Signaling 3922 No IGFRb IGFR BETA Cell Signaling 3027 No IRS1 IRS1 Upstate No IRS1.pS307 IRS1 S307 Upstate No JNK JNK Santa Cruz 474 No JNK.pT183.Y185 JNK T183 Y185 Cell Signaling 9251 No LKB1.pS428 LKB1 S428 Cell Signaling 3051 No MAPK.pT202.Y204 ERK1/ERK2 T202 Y204 Cell Signaling 4377 No MAPK.pT202.Y204 ERK1/ERK2 T202 Y204 Cell Signaling 9101 No MAPK1 ERK2 Santa Cruz 154 MAPK14 P38 MAPK Cell Signaling 9212 MAPK14.pT180.Y1 82 P38 MAPK T180 Y182 Cell Signaling 9211 MCAM MCAM BD Pharmingen No

3 MCL1 MCL1 Epitomics 1239 No MEK1 MEK Epitomics No MEK1&2.pS217.S2 21 MEK S217 S221 Cell Signaling 9121 No MGMT MGMT Chemicon No mtor.ps2448 mtor S2448 Cell Signaling 2971 No p16 P16 Epitomics 1712 No p21 P21 Santa Cruz 397 No p27 P27 Santa Cruz 528 No P27 P27 BD Pharmingen No p53 P53 Cell Signaling 9282 No P70S6K P70S6K Cell Signaling 9205 P70S6K.pT389 P70S6K T389 Epitomics 1494 PAI1 PAI1 BD Pharmingen No PARP.C PARP Cell Signaling 9541 No PDK1 PDK1 Cell Signaling 3062 No PDK1.pS241 PDK1 S241 Cell Signaling 3061 No PI3K.p110 PI3K P110 ALPHA Epitomics 1683 No PR PROGESTERONE RECEPTOR Epitomics prb RB Cell Signaling 9309 No PRKCA PROTEIN KINASE C ALPHA Upstate PRKCA.pS567 PROTEIN KINASE C ALPHA S567 Upstate No PTEN PTEN Cell Signaling 9552 RAB25 RAB25 Provided by Dr. Kwai Wa Cheng RPS6KA1 P90 RSK Cell Signaling 9345 No RPS6KA1.pT389.S 363 P90 RSK T389 S363 Cell Signaling 9344 No RPS6KB1.pS235.S 236 S6 S236 S236 Cell Signaling 2211 RPS6KB1.pS240.S 244 S6 S240 S244 Cell Signaling 2215 S6 S6 Cell Signaling 2217 No SGK SGK Cell Signaling 3272 No

4 SGK.pS78 SGK S78 Cell Signaling 3271 No SMN SURVIVAL OF MOTOR NEURONS Santa Cruz No SRC SRC Upstate No SRC.pY416 SRC Y416 Cell Signaling 2101 No SRC.pY527 SRC Y527 Cell Signaling 2105 No STAT3 STAT3 Upstate No STAT3.pS727 STAT3 S727 Cell Signaling 9134 No STAT3.pY705 STAT3 Y705 Cell Signaling 9131 No STAT5 STAT5 Epitomics 1289 No STAT5.pY694 STAT5 Y694 Epitomics 1208 No STAT6.pY641 STAT6 Y641 Cell Signaling 9361 No STATHMIN STATHMIN Epitomics 1971 No TAU TAU Upstate No TGM2 TRANSGLUTAMINASE Neomarkers MS300P No TSC2 TUBERIN Epitomics No TSC2.pT1462 TUBERIN T1462 Cell Signaling 3617 No VEGFR1 VEGFR1 Epitomics No VEGFR2 VEGFR2 Cell Signaling 2479 No

5 Supplementary Table 2. Association study of mutation status with cancer cell types of NCI60 cell lines. 9 group chi-square test and Fisher s exact test of mutation status against cancer cell types were performed. Mutation Total Homozygous exact test exact test P P RB PTEN PIK3CA NA 1 LKB APC* SMAD VHL RAS B-RAF* FLT NA 1 BRCA NA 1 BRCA2* NA 1 HER NA 1 EGFR PDGFR-a NA 1 B-CATENIN NA 1 *Mutation status showing significant enrichments in each specific cancer cell types.

6 Supplementary Table 3. Association study of mutation status with integrated RPPA data of NCI60 cell lines (I). Each cluster was compared to the rest of cell lines by 2 group chi-square test and Fisher s exact test to identify unique enrichment of mutations in each specific cluster. All mutation status including homozygous and heterozygous mutations was counted to estimate enrichment. Total Mutation Cluster 1 vs. Other Cluster 2 vs. Other Cluster 3 vs. Other Cluster 4 vs. Other Cluster 5 vs. Other P P RB PTEN PIK3CA LKB APC* SMAD4* VHL RAS B-RAF* FLT BRCA BRCA2* HER EGFR PDGFR-a B-CATENIN * Mutations showing significant enrichments in each cluster.

7 Supplementary Table 4. Association study of mutation status with integrated RPPA data of NCI60 cell lines (II). Each cluster was compared to the rest of cell lines by 2 group chi-square test and Fisher s exact test to identify unique enrichment of mutations in each specific cluster. Only the homozygous mutation was counted to estimate enrichment. Homozygous Mutation Cluster 1 vs. Other Cluster 2 vs. Other Cluster 3 vs. Other Cluster 4 vs. Other Cluster 5 vs. Other P P RB PTEN* PIK3CA NA NA NA NA NA LKB APC SMAD VHL RAS B-RAF* FLT3 NA NA NA NA NA BRCA1 NA NA NA NA NA BRCA2 NA NA NA NA NA HER2 NA NA NA NA NA EGFR PDGFR-a NA NA NA NA NA B-CATENIN NA NA NA NA NA * Mutations showing significant enrichments in each cluster.

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