Supplementary Table 5. List of the 220 most frequently amplified in this study. The table includes their chromosomal location, the amplification frequency in ER-positive female breast cancer with associated p-value for difference in proportions, the preference for surrogate intrinsic molecular subtype, and associations with clinical, pathological and genetic characteristics. Potentially druggable categories, clinical actionability and known drug interactions are indicated per gene.

Gene Full name chr location % amp in FFPE % amps in FF total % amp % amp ER+ FBC* p-value MBC vs ER+ FBC** % in lumA-like % in lumB-like p-value BRCA2 germline Age Hist type ER status PR status HER2 status Grade MAI Size LN SNV load PIK3CA mut KM (OS)*** KM (5Y OS)*** druggable gene category# clinically actionable?## known drug interactions?### THBS1 thrombospondin 1 15q14 37% 9% 30% 0.1% <0.0001 23% 35% 0.128 ns ns ns ns ns ns ns ns ns ns ns ns 0.642 p=0.832 cell surface, tumor suppressor, drug resistance, external side of plasma membrane no none PRKDC , DNA-activated, catalytic polypeptide 8q11.21 35% 7% 27% 10.9% <0.0001 26% 30% 0.595 ns ns ns ns ns ns ns ns ns ns ns ns 0.838 p=0.903 ( threonine) kinase, druggable genome, PI3 kinase, tumor suppressor, TF complex, TF binding, DNA repair yes DNA-PK INHIBITOR V (DNA-PK inhibitor); WORTMANNIN (PI3K inhibitor); SF1126 (PI3 kinase/mTOR inhibitor) TBX3 T-box 3 12q24.21 34% 7% 27% 0.1% <0.0001 20% 35% 0.053 ns ns ns ns ns ns ns ns ns ns ns ns 0.439 p=0.264 tumor suppressor, TF binding yes none ASAP1 ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 8q24.21-q24.22 32% 7% 25% 20.2% 0.1691 20% 32% 0.123 p=0.001 ns ns ns ns ns ns ns ns ns ns ns 0.834 p=0.748 no no none RAD21 RAD21 cohesin complex component 8q24.11 32% 4% 24% 21.8% 0.4851 18% 33% 0.051 ns ns ns ns ns ns ns ns ns ns ns ns 0.908 p=0.842 DNA repair no none UBR5 Ubiquitin Protein E3 Component N-Recognin 5 8q22.3 29% 11% 24% 18.8% 0.1142 20% 32% 0.123 p=0.002 ns ns ns ns ns 0.037 (high) 0.047 (high) ns ns ns ns p=0.228 p=0.855 DNA repair no none ARNT aryl hydrocarbon receptor nuclear translocator 1q21.3 29% 9% 24% 18.6% 0.1483 24% 23% 0.905 ns ns ns ns ns p=0.003 (pos) ns ns ns ns ns p=0.011 (mut) 0.089 (poor; 17) p=0.113 TF complex, TF binding no none LAMC1 laminin subunit gamma 1 1q25.3 30% 9% 24% 23.9% 0.9584 23% 25% 0.765 ns ns ns ns ns p=0.003 (pos) ns p=0.002 (high) ns ns ns ns 0.623 p=0.667 no no none SMYD2 SET and MYND domain containing 2 1q32.3 32% 2% 24% 26.6% 0.4640 20% 32% 0.123 ns ns ns ns ns ns ns p=0.007 (high) ns ns ns ns 0.023 (poor; 19) p=0.068 (poor; 14) histone modification, methyl no none SMYD3 SET and MYND domain containing 3 1q44 30% 4% 23% 24.0% 0.7943 23% 25% 0.765 ns ns ns ns ns ns p=0.023 (high) p=0.0004 (high) ns ns ns p=0.024 (mut) 0.019 (poor; 20) p=0.045 (poor; 15) histone modification, methyl transferase no none ANK1 Ankyrin 1 8p11.21 22% 20% 22% 11.5% 0.0003 20% 17% 0.660 ns ns ns ns ns ns ns ns ns ns ns ns p=0.661 p=0.826 no no none CREBBP CREB Binding Protein 16p13.3 25% 13% 22% 8.9% <0.0001 23% 20% 0.709 ns ns ns ns ns ns ns ns ns ns ns p=0.019 (no mut) p=0.590 p=0.234 tumor suppressor; TF complex; histone modification; TF binding yes ISCHEMIN; DB08655 (CREBBP inhibitors) KDM5B lysine demethylase 5B 1q32.1 30% 2% 22% 27.0% 0.2269 24% 23% 0.905 ns ns ns ns ns ns ns p=0.0004 (high) ns ns ns ns 0.149 p=0.107 histone modification no PBIT (histone demethylase inhibitor) SCYL3 SCY1 like pseudokinase 3 1q24.2 31% 0% 22% 22.4% 0.9574 20% 28% 0.256 ns ns ns ns ns ns ns p=0.009 (high) ns ns ns ns 0.007 (poor; 18) p=0.022 (poor; 14) (serine threonine) kinase, druggable genome no none TSC2 2 16p13.3 23% 20% 22% 9.4% <0.0001 23% 18% 0.543 ns ns ns ns ns ns ns ns ns ns ns ns p=0.544 p=0.067 (better; 4) tumor suppressor yes none ASH2L ASH2 Like Histone Lysine Methyltransferase Complex Subunit 8p11.23 24% 13% 21% 15.0% 0.0459 14% 30% 0.025 ns ns ns ns 0.042 (neg) ns ns ns ns ns ns ns p=0.701 p=0.619 B30_2 SPRY domain; druggable genome; histone modification no none CAPN2 2 1q41 29% 2% 21% 25.3% 0.3288 27% 17% 0.153 ns ns ns ns ns ns ns ns ns ns ns p=0.013 (mut) 0.329 p=0.681 , druggable genome no none CCND1 Cyclin D1 11q13.3 25% 11% 21% 19.4% 0.5560 17% 27% 0.172 ns ns ns ns ns ns ns 0.018 (high) ns ns ns ns p=0.265 p=0.128 kinase; tumor suppressor; drug resistance; TF binding yes TAMOXIFEN (SERM); ABEMACICLIB; RIBOCICLIB (CDK4/6 inhibitors) COL14A1 collagen type XIV alpha 1 chain 8q24.12 27% 7% 21% 21.0% 0.8915 18% 27% 0.253 ns ns ns ns ns ns p=0.044 (high) ns ns ns ns ns 0.545 p=0.775 druggable genome no none ELF3 E74 Like ETS Transcription Factor 3 1q32.1 26% 11% 21% 26.8% 0.1808 21% 20% 0.867 ns ns ns ns ns 0.027 (pos) ns ns ns ns ns p=0.013 (mut) p=0.068 (poor; 14) p=0.312 no no none ERBB2 Erb-B2 Receptor Tyrosine Kinase 2 17q12 24% 13% 21% 10.7% 0.0002 21% 22% 0.950 ns ns ns ns ns 0.002 (pos) ns ns p=0.008 (large) ns ns p=0.008 (mut) p=0.090 (poor; 14) p=0.126 (tyrosine) kinase; druggable genome yes AFATINIB; NERATINIB; LAPATINIB; DACOMITINIB; SAPITINIB; BMS-599626; MUBRITINIB (tyrosine kinase inhibitors) etc. OBSCN , Cytoskeletal And -Interacting RhoGEF 1q42.13 21% 20% 21% 24.9% 0.3799 26% 12% 0.044 ns ns ns ns ns ns ns ns p=0.008 (large) ns ns ns p=0.135 p=0.451 (serine threonine) kinase; druggable genome no none WHSC1L1 Nuclear Receptor Binding SET Domain Protein 3 8p11.23 24% 16% 21% 14.8% 0.0387 17% 25% 0.248 ns ns ns ns ns ns ns ns ns ns ns ns p=0.830 p=0.661 histone modification; methyl transferase no none COL1A1 Collagen Type I Alpha 1 Chain 17q21.33 23% 13% 21% 6.7% <0.0001 18% 17% 0.823 ns ns ns ns ns ns ns ns p=0.012 (large) ns p=0.035 (high) ns p=0.035 (poor; 15) p=0.091 (poor; 11) drug resistance no HALOFUGINONE (COL1A1/MMP2 inhibitor); ZOLEDRONIC ACID (bisphosphonate) FGFR1 Fibroblast Growth Factor Receptor 1 8p11.23 23% 13% 21% 14.6% 0.0324 15% 23% 0.243 ns ns ns ns ns ns ns ns ns ns ns ns p=0.702 p=0.296 druggable genome; (tyrosine) kinase; tumor suppressor yes PONATINIB; NINTEDANIB; DOVITINIB; SORAFENIB; LENVATINIB; ENMD-2076 (tyrosine kinase inhibitors) etc. IKBKB Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Beta 8p11.21 22% 16% 21% 10.7% 0.0002 20% 20% 0.966 ns ns ns ns ns ns ns ns ns ns p=0.011 (high) ns p=0.035 (better; 6) p=0.039 (better; 3) druggable genome; (serine threonine) kinase; drug resistance no AURANOFIN; SULFASALAZINE (antirheumatic agents) LAMB3 Laminin Subunit Beta 3 1q32.2 21% 18% 21% 27.6% 0.1268 23% 15% 0.270 ns ns ns ns ns 0.021 (pos) ns ns ns ns ns ns p=0.808 p=0.471 no no none LRP2 LDL Receptor Related Protein 2 2q31.1 23% 13% 21% 0.0% <0.0001 20% 18% 0.846 ns ns ns ns ns ns ns ns ns ns ns ns p=0.673 p=0.812 no no none PARP1 poly(ADP-ribose) polymerase 1 1q42.12 26% 7% 21% 25.1% 0.3537 23% 18% 0.543 ns ns ns ns ns ns ns ns ns ns ns ns 0.111 p=0.200 druggable genome, TF complex, TF binding, DNA repair yes VELIPARIB; RUCAPARIB; OLAPARIB; 3-METHOXYBENZAMIDE; NU1025; NICOTINAMIDE (PARP inhibitors); INIPARIB (unknown) etc TEX14 testis expressed 14, intercellular bridge forming factor 17q22 25% 9% 21% 9.1% <0.0001 14% 25% 0.105 ns ns ns ns p=0.004 (neg) p=0.001 (pos) p=0.040 (high) ns ns ns ns ns 0.71 p=0.895 (tyrosine) kinase, tumor suppressor, druggable genome no none CIT Citron Rho-Interacting Serine/Threonine Kinase 12q24.23 20% 18% 20% 0.2% <0.0001 18% 17% 0.823 ns ns ns ns ns ns ns ns ns ns ns ns p=0.154 p=0.802 (serine threonine) kinase; tumor suppressor; druggable genome no none CSMD3 CUB and Sushi multiple domains 3 8q23.3 25% 7% 20% 21.3% 0.7234 15% 27% 0.111 p=0.001 ns ns ns ns ns ns p=0.028 (high) ns ns ns ns 0.539 p=0.970 no no none LAMA5 Laminin Subunit Alpha 5 20q13.33 20% 18% 20% 7.0% <0.0001 20% 18% 0.846 ns ns ns ns ns ns ns ns ns ns ns ns p=0.308 p=0.232 no no none MAP3K15 -Activated Protein Kinase Kinase Kinase 15 Xp22.12 18% 22% 20% 0.7% <0.0001 23% 12% 0.102 ns ns ns ns ns ns ns ns ns ns ns ns p=0.793 p=0.761 (serine threonine) kinase; druggable genome no none PTK2 protein tyrosine kinase 2 8q24.3 28% 0% 20% 18.5% 0.6682 20% 22% 0.785 ns ns ns ns ns ns ns ns ns ns ns ns 0.359 p=0.303 (tyrosine) kinase, druggable genome no MASITINIB; ENMD-2076 (tyrosine kinase inhibitors) FZD6 frizzled class receptor 6 8q22.3 26% 2% 19% 18.7% 0.8642 17% 23% 0.349 p=0.010 ns ns ns ns ns ns ns ns ns ns ns 0.735 p=0.499 G protein coupled receptor, druggable genome, cell surface no none HDAC5 Histone Deacetylase 5 17q21.31 20% 16% 19% 0.8% <0.0001 23% 12% 0.102 ns ns ns ns ns ns ns ns p=0.009 (large) ns ns ns p=0.154 p=0.959 drug resistance; histone modification; TF binding no BELINOSTAT; DACINOSTAT; GIVINOSTAT; PANOBINOSTAT; ROMIDEPSIN; VORINOSTAT (HDAC inhibitors) etc. NEK10 NIMA related kinase 10 3p24.1 27% 0% 19% 0.3% <0.0001 17% 23% 0.349 ns ns ns ns ns ns ns ns ns ns ns ns 0.606 p=0.766 (serine threonine) kinase, druggable genome, tumor suppressor no none RNF213 ring finger protein 213 17q25.3 25% 7% 19% 3.9% <0.0001 23% 17% 0.394 ns ns ns ns ns ns ns ns ns ns ns ns 0.597 p=0.781 no no none DUSP10 dual specificity phosphatase 10 1q41 25% 2% 19% 25.8% 0.0614 15% 23% 0.243 ns ns ns ns ns ns ns ns ns ns p=0.005 (high) p=0.013 (mut) 0.041 (poor; 13) p=0.111 protein phosphatase, druggable genome no none EEF2K eukaryotic elongation factor 2 kinase 16p12.2 22% 9% 19% 7.5% <0.0001 23% 13% 0.173 ns ns ns ns ns ns ns ns ns ns ns ns 0.805 p=0.486 (serine threonine) kinase, druggable genome no none EXT1 exostosin glycosyltransferase 1 8q24.11 22% 9% 19% 21.3% 0.4450 12% 27% 0.038 ns ns ns ns ns ns ns ns ns ns ns ns 0.785 p=0.873 growth factor yes none KAT8 Lysine Acetyltransferase 8 16p11.2 20% 13% 19% 7.3% <0.0001 15% 20% 0.474 ns ns ns ns ns ns ns ns ns ns ns ns p=0.571 p=0.911 histone modification; TF binding no none MAST4 microtubule associated serine/threonine kinase family member 4 5q12.3 23% 7% 19% 0.5% <0.0001 17% 22% 0.475 ns ns ns ns ns ns ns ns ns ns ns ns 0.717 p=0.349 druggable genome, (serine threonine) kinase no none NTRK1 Neurotrophic Receptor Tyrosine Kinase 1 1q23.1 16% 20% 19% 20.8% 0.5270 23% 10% 0.056 ns ns ns ns ns ns ns ns p=0.001 (large) ns ns ns p=0.489 p=0.765 (tyrosine) kinase; druggable genome; cell surface; drug resistance yes IMATINIB; LESTAURTINIB; REGORAFENIB; DOVITINIB; ENMD-2076 (tyrosine kinase inhibitors); AMITRIPTYLINE (antidepressant) PTPN1 protein tyrosine phosphatase, non-receptor type 1 20q13.13 22% 9% 19% 6.5% <0.0001 12% 23% 0.098 ns ns ns ns p=0.005 (neg) ns ns ns ns ns ns ns 0.668 p=0.790 protein phosphatase, druggable genome no TRODUSQUEMINE (PTP1B inhibitor); DB02014; DB02615; SP7343-SP7964; PNU177836; DB07263 etc TGFB2 transforming growth factor beta 2 1q41 25% 2% 19% 26.6% 0.0398 17% 23% 0.349 ns ns ns ns ns ns ns p=0.002 (high) ns ns ns ns 0.195 p=0.025 (poor; 12) (serine threonine) kinase, tumor suppressor, drug resistance, growth factor no none ASH1L ASH1 like histone lysine methyltransferase 1q22 22% 7% 18% 20.6% 0.4393 18% 18% 0.982 ns ns ns ns ns ns ns p=0.014 (high) ns ns ns ns 0.060 (poor; 16) p=0.047 (poor; 12) methyl transferase, histone modification no none CBLC Cbl Proto- C 19q13.32 18% 18% 18% 0.5% <0.0001 20% 10% 0.129 ns p=0.040 (old) ns ns ns ns ns ns ns ns p=0.017 (high) ns p=0.824 p=0.328 no no none CDC42BPA CDC42 binding protein kinase alpha 1q42.13 23% 4% 18% 25.2% 0.0559 15% 22% 0.344 ns ns ns ns ns ns ns p=0.014 (high) ns ns ns ns 0.963 p=0.829 (serine threonine) kinase, druggable genome no none FLNB Filamin B 3p14.3 18% 16% 18% 0.1% <0.0001 15% 15% 0.981 ns ns ns ns ns ns ns ns ns ns ns ns p=0.451 p=0.479 no no none POU2F1 POU class 2 homeobox 1 1q24.2 23% 7% 18% 22.4% 0.2168 20% 17% 0.660 ns ns ns ns ns ns ns ns ns ns ns ns 0.139 p=0.337 no no none SNTB1 syntrophin beta 1 8q24.12 23% 4% 18% 21.2% 0.3524 14% 22% 0.236 ns ns ns ns ns ns ns ns ns ns ns ns 0.536 p=0.235 no no none WNK4 WNK lysine deficient protein kinase 4 17q21.2 22% 7% 18% 1.1% <0.0001 20% 13% 0.338 ns ns ns ns ns ns ns ns ns ns ns ns 0.599 p=0.980 (serine threonine) kinase, druggable genome no none ZNF703 zinc finger protein 703 8p11.23 22% 9% 18% 16.2% 0.6301 11% 23% 0.056 ns ns ns ns p=0.006 (neg) ns ns ns ns ns ns ns 0.164 p=0.312 tumor suppressor, TF binding yes none COL4A6 Collagen type IV alpha 6 chain Xq22.3 14% 22% 17% 0.4% <0.0001 20% 10% 0.129 ns ns ns ns ns ns ns ns ns ns ns ns p=0.270 p=0.143 no no none EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1 8p11.23 20% 9% 17% 15.2% 0.5785 11% 23% 0.056 ns ns ns ns p=0.001 (neg) ns ns ns p=0.015 (large) ns ns ns 0.957 p=0.574 tumor suppressor no none GATA3 GATA Binding Protein 3 10p14 19% 11% 17% 1.2% <0.0001 12% 18% 0.330 ns ns ns ns ns ns ns ns ns ns ns ns p=0.087 (poor; 11) p=0.471 tumor suppressor; TF complex; TF binding; drug resistance yes none KAT6A lysine acetyltransferase 6A 8p11.21 20% 9% 17% 11.4% 0.0540 12% 18% 0.330 ns ns ns ns ns ns ns ns ns ns ns ns 0.946 p=0.923 histone modification, TF binding yes none MAP3K3 mitogen-activated protein kinase kinase kinase 3 17q23.3 21% 9% 17% 8.7% 0.0015 14% 20% 0.338 ns ns ns ns p=0.025 (neg) ns p=0.015 (high) ns ns ns ns ns 0.248 p=0.691 druggable genome, (serine threonine) kinase no none MAPK8IP3 Mitogen-activated protein kinase 15 8q24.3 15% 18% 17% 9.9% 0.0099 23% 8% 0.027 ns ns ns ns ns ns ns ns ns ns p=0,049 (high) ns p=0.335 p=0.061 (better; 2) kinase no none MVP Major Vault Protein 16p11.2 19% 11% 17% 7.5% 0.0001 20% 12% 0.218 ns ns ns ns ns ns ns ns p=0.034 (large) ns ns ns p=0.971 p=0.345 no no none NOTCH3 Notch 3 19p13.12 13% 24% 17% 1.9% <0.0001 21% 7% 0.020 ns ns ns ns ns ns ns ns p=0.034 (large) ns ns ns p=0.601 p=0.452 no yes RO4929097 (Notch inhibitor) PHKA2 regulatory subunit alpha 2 Xp22.13 15% 18% 17% 0.7% <0.0001 18% 10% 0.190 ns ns ns ns ns ns ns ns ns ns ns ns p=0.755 p=0.655 (serine threonine) kinase no none PPM1D Protein Phosphatase, Mg2+/Mn2+ Dependent 1D 17q23.2 19% 13% 17% 10.4% 0.0187 9% 25% 0.017 ns ns ns ns p=0.025 (neg) p=0.015 (pos) p=0.001 (high) ns ns ns ns ns p=0.678 p=0.384 protein phosphatase no none RRM2B ribonucleotide reductase regulatory TP53 inducible subunit M2B 8q22.3 22% 4% 17% 19.2% 0.5329 15% 20% 0.474 p=0.007 ns ns ns ns p=0.017 (pos) ns p=0.003 (high) ns ns ns ns 0.446 p=0.653 DNA repair no GEMCITABINE (antimetabolite and deoxycytidine analogue); MOTEXAFIN GADOLINIUM (radio/chemo sensitizer); CLADRIBINE (purine analog) SMG1 SMG1, nonsense mediated mRNA decay associated PI3K related kinase 16p12.3 21% 7% 17% 7.6% 0.0002 15% 20% 0.474 ns ns ns ns ns ns ns ns ns ns ns ns 0.337 p=0.499 PI3 kinase, (serine threonine) kinase, druggable genome, DNA repair no none TP53BP2 tumor protein p53 binding protein 2 1q41 23% 2% 17% 24.8% 0.0426 17% 20% 0.629 ns ns ns ns ns ns p=0.023 (high) ns ns ns ns p=0.008 (mut) 0.067 (poor; 15) p=0.126 tumor suppressor, TF binding no none ADCK5 AarF Domain Containing Kinase 5 8q24.3 18% 11% 16% 18.1% 0.6018 15% 18% 0.632 ns ns ns ns ns ns ns ns ns ns ns ns p=0.361 p=0.205 (serine threonine) kinase; druggable genome no none BMP7 bone morphogenetic protein 7 20q13.31 20% 7% 16% 7.3% 0.0002 18% 13% 0.457 ns ns ns ns ns ns ns ns ns ns p=0.026 (high) p=0.037 (mut) 0.401 p=0.916 tumor suppressor, growth factor no none CAMK2B Calcium/calmodulin dependent protein kinase II beta 7p13 12% 22% 16% 1.6% <0.0001 18% 7% 0.053 ns ns ns ns ns ns ns ns p=0.024 (large) ns ns ns p=0.651 p=0.651 druggable genome; (serine threonine) kinase; tumor suppressor no none CARS Cysteinyl-tRNA synthetase 11p15.4 14% 18% 16% 0.7% <0.0001 18% 8% 0.106 ns ns ns ns ns ns ns ns ns ns ns ns p=0.901 p=0.446 no no none DNAH11 Dynein Axonemal Heavy Chain 11 7p15.3 16% 13% 16% 1.9% <0.0001 17% 12% 0.423 p=0.003 ns ns ns ns ns ns ns ns ns ns ns p=0.333 p=0.120 no no none DSTYK Dual Serine/Threonine And Tyrosine Protein Kinase 1q32.1 18% 11% 16% 28.0% 0.0034 15% 17% 0.816 ns ns ns ns ns ns ns ns ns ns ns p=0.020 (mut) p=0.280 p=0.624 (serine threonine) kinase; druggable genome; tyrosine kinase no none EHMT2 Euchromatic histone lysine methyltransferase 2 6p21.33 12% 24% 16% 0.5% <0.0001 21% 5% 0.008 ns ns ns ns p=0.020 (pos) ns ns ns ns ns ns ns p=0.539 p=0.800 drug resistance; histone modification; methyl transferase no BIX-01294; UNC0638; UNC0642 (HMT inhibitors) ERGIC3 ERGIC and golgi 3 20q11.22 20% 7% 16% 2.7% <0.0001 14% 17% 0.635 ns ns ns ns ns p=0.013 (pos) ns ns ns ns ns ns 0.18 p=0.409 no no none KDM5C Lysine demethylase 5C Xp11.22 11% 24% 16% 0.3% <0.0001 18% 8% 0.106 ns ns ns ns ns ns p=0.049 (low) ns ns ns ns ns p=0.651 p=0.114 histone modification yes PBIT (KDM5 inhibitor) PGPEP1 Pyroglutamyl-peptidase I 19p13.11 16% 13% 16% 1.4% <0.0001 20% 8% 0.069 ns ns ns ns ns ns ns p=0.049 (low) ns ns ns ns p=0.080 (poor; 10) p=0.310 protease; druggable genome no none PIK3C2B Phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta 1q32.1 16% 13% 16% 28.3% 0.0027 15% 15% 0.981 ns ns ns ns ns p=0.011 (pos) ns p=0.026 (high) ns ns ns p=0.001 (mut) p=0.131 p=0.155 PI3 kinase; druggable genome; (lipid) kinase no GDC-0941; GDC-0980; GSK2636771; PI-103; PKI-587; QUERCETIN; SF1126; XL147 (kinase inhibitors) PSEN2 Presenilin 2 1q42.13 15% 16% 16% 25.2% 0.0213 20% 7% 0.032 ns ns ns ns ns ns ns ns ns ns ns ns p=0.419 p=0.806 cell surface; protease; druggable genome no none PTPN7 protein tyrosine phosphatase, non-receptor type 7 1q32.1 19% 9% 16% 27.0% 0.0067 20% 10% 0.129 ns ns ns ns ns ns ns ns ns ns ns ns 0.026 (poor; 12) p=0.186 protein phosphatase, druggable genome no none SETD1A SET domain containing 1A 16p11.2 16% 13% 16% 7.3% 0.0002 21% 8% 0.044 ns ns ns ns ns ns ns ns ns ns ns ns p=0.796 p=0.259 methyl transferase; histone modification no none SRPK2 SRSF protein kinase 2 7q22.3 14% 18% 16% 0.5% <0.0001 14% 15% 0.827 ns ns ns ns ns ns ns ns ns ns ns ns p=0.793 p=0.669 (serine threonine) kinase; druggable genome; tumor suppressor no DB04395 (ATPase inhibitor); PURVALANOL (CDK/MAPK inhibitor) THBS3 Thrombospondin 3 1q22 16% 13% 16% 21.2% 0.1792 18% 12% 0.307 ns ns ns ns ns ns ns ns ns ns ns p=0.028 (mut) p=0.092 (poor; 12) p=0.510 no no none TPX2 TPX2, microtubule nucleation factor 20q11.21 22% 2% 16% 1.9% <0.0001 18% 17% 0.823 ns ns ns ns ns ns ns ns ns ns ns ns 0.157 p=0.219 tumor suppressor no none ADCK3 AarF Domain-Containing Protein Kinase 3 1q42.13 13% 18% 16% 25.3% 0.0200 18% 10% 0.190 ns ns ns ns ns ns ns ns ns ns p=0.044 (high) ns p=0.882 p=0.727 (serine threonine) kinase; druggable genome no none ERBB3 Erb-b2 receptor tyrosine kinase 3 12q13.2 16% 11% 16% 0.7% <0.0001 17% 10% 0.274 ns ns ns ns ns ns ns ns ns ns ns ns p=0.709 p=0.662 (tyrosine) kinase; druggable genome yes SAPITINIB; LAPATINIB; DACOMITINIB; GEFITINIB; POZIOTINIB (EGFR/HER inhibitors) ERN1 endoplasmic reticulum to nucleus signaling 1 17q23.3 21% 4% 16% 8.7% 0.0036 12% 18% 0.330 ns ns ns ns p=0.014 (neg) ns ns ns ns ns ns ns 0.074 (poor; 13) p=0.524 druggable genome, (serine threonine) kinase, tumor suppressor no none ERN2 endoplasmic reticulum to nucleus signaling 2 16p12.2 18% 9% 16% 7.4% 0.0003 17% 13% 0.602 ns ns ns ns ns ns ns ns ns ns ns ns 0.616 p=0.347 druggable genome, (serine threonine) kinase, tumor suppressor no none ESPL1 Extra spindle pole bodies like 1, 12q13.13 14% 18% 16% 0.1% <0.0001 18% 10% 0.190 ns ns ns ns ns ns ns ns ns ns ns ns p=0.832 p=0.397 tumor suppressor; protease; druggable genome no none GNAS GNAS complex locus 20q13.32 19% 7% 16% 8.1% 0.0013 15% 15% 0.981 ns ns ns ns ns ns ns p=0.037 (low) ns ns p=0.013 (high) ns 0.236 p=0.130 drug resistance yes FORSKOLIN (adenylyl cyclase activator) HDAC6 Histone deacetylase 6 Xp11.23 12% 20% 16% 0.3% <0.0001 17% 12% 0.423 ns ns ns ns ns ns ns ns ns ns ns ns p=0.929 p=0.887 histone modification no VORINOSTAT; BELINOSTAT; PANOBINOSTAT; ROMIDEPSIN; DACINOSTAT; GIVINOSTAT; RESMINOSTAT etc (HDAC inhibitors) LAMC2 laminin subunit gamma 2 1q25.3 19% 9% 16% 23.8% 0.0480 20% 10% 0.129 ns ns ns ns ns ns ns ns ns ns ns ns 0.198 p=0.489 no no none LGR6 Leucine rich repeat containing G protein-coupled receptor 6 1q32.1 16% 11% 16% 26.8% 0.0077 18% 12% 0.307 ns ns ns ns ns p=0.011 (pos) ns p=0.026 (high) ns ns ns ns p=0.762 p=0.606 G protein coupled receptor; druggable genome no none NPR1 Natriuretic peptide receptor 1 1q21.3 15% 13% 16% 20.4% 0.2547 18% 8% 0.106 ns ns ns ns ns ns ns ns ns ns ns ns p=0.722 p=0.250 druggable genome; kinase; G protein coupled receptor no ISOSORBIDE DINITRATE; ERYTHRITYL TETRANITRATE; NITROGLYCERIN; NITROPRUSSIDE etc (vasodilator agents) PRKAB1 protein kinase AMP-activated non-catalytic subunit beta 1 12q24.23 19% 7% 16% 0.3% <0.0001 14% 18% 0.471 ns p=0.047 (young) ns ns ns ns ns ns ns ns p=0.044 (high) ns 0.21 p=0.270 (serine threonine) kinase, tumor suppressor no METFORMIN (mitochondrial complex I inhibitor; mTOR inhibitor) PTPN14 protein tyrosine phosphatase, non-receptor type 14 1q32.3-q41 19% 7% 16% 26.6% 0.0088 18% 10% 0.190 ns ns ns ns ns ns ns p=0.026 (high) ns ns ns ns 0.836 p=0.525 protein phosphatase, druggable genome no none RBPJL Recombination signal binding protein for immunoglobulin kappa J region like 20q13.12 16% 11% 16% 4.7% <0.0001 17% 12% 0.423 ns ns ns ns ns ns ns ns p=0.037 (large) ns ns ns p=0.964 p=0.228 TF complex no none RPTOR Regulatory associated protein of MTOR complex 1 17q25.3 14% 18% 16% 3.8% <0.0001 15% 12% 0.567 ns ns ns ns ns ns ns ns p=0.024 (large) ns ns ns p=0.956 p=0.243 tumor suppressor; TF binding yes AZD8055; OSI-027; SIROLIMUS; TEMSIROLIMUS (mTOR inhibitors) RUNX1T1 RUNX1 translocation partner 1 8q21.3 16% 11% 16% 18.6% 0.5091 14% 17% 0.635 p=0.023 ns ns ns ns ns ns ns ns ns ns ns p=0.551 p=0.190 no no none SENP2 SUMO1/sentrin/SMT3 specific peptidase 2 3q27.2 16% 11% 16% 1.9% <0.0001 11% 17% 0.320 ns ns ns ns ns ns ns p=0.038 (high) ns ns ns ns p=0.221 p=0.317 tumor suppressor; protease; druggable genome no none TMEM67 transmembrane protein 67 8q22.1 22% 0% 16% 18.8% 0.4747 12% 20% 0.227 ns ns ns ns ns p=0.013 (pos) ns ns ns ns ns ns 0.66 p=0.205 tumor suppressor no none TRAF5 TNF receptor associated factor 5 1q32.3 22% 0% 16% 25.0% 0.0240 11% 23% 0.056 ns ns ns ns ns ns ns p=0.004 (high) ns ns ns p=0.032 (mut) 0.388 p=0.299 no no none TRIO Trio Rho guanine nucleotide exchange factor 5p15.2 16% 11% 16% 2.9% <0.0001 17% 13% 0.602 ns ns ns ns ns ns ns ns ns p=0.049 (pos) ns ns p=0.414 p=0.839 (serine threonine) kinase; druggable genome no none DKK4 Dickkopf WNT signaling pathway inhibitor 4 8p11.21 15% 11% 15% 10.3% 0.1049 15% 12% 0.567 ns ns ns ns ns ns p=0.034 (low) ns ns ns p=0.023 (high) ns p=0.113 p=0.066 (better; 2) no no none EPHB4 EPH receptor B4 7q22.1 13% 16% 15% 0.6% <0.0001 18% 7% 0.053 ns ns ns ns ns ns ns ns p=0.037 (large) ns ns ns p=0.313 p=0.914 (tyrosine) kinase; druggable genome no DB07255; DB07249 (EphB4 small molecule inhibitors) EXO1 exonuclease 1 1q43 21% 0% 15% 24.2% 0.0135 15% 17% 0.816 ns ns ns ns ns ns p=0.003 (high) p=0.0003 (high) ns ns ns ns 0.552 p=0.186 DNA repair no none FADD Fas associated via death domain 11q13.3 16% 11% 15% 18.1% 0.3375 9% 20% 0.081 ns ns ns ns ns ns ns p=0.0001 (high) ns ns ns ns p=0.217 p=0.157 no no none HCK HCK proto-oncogene, Src family tyrosine kinase 20q11.21 15% 11% 15% 1.7% <0.0001 17% 12% 0.423 ns ns ns ns ns ns ns ns ns ns ns ns p=0.918 p=0.932 (tyrosine) kinase; druggable genome no BOSUTINIB; MASITINIB (tyrosine kinase inhibitors) IKBKE Inhibitor of nuclear factor kappa B kinase subunit epsilon 1q32.1 15% 11% 15% 27.7% 0.0012 17% 10% 0.274 ns ns ns ns ns ns ns ns ns ns ns ns p=0.449 p=0.659 (serine threonine) kinase; druggable genome yes none MAST3 Microtubule associated serine/threonine kinase 3 19p13.11 11% 22% 15% 1.5% <0.0001 18% 7% 0.053 ns ns ns ns ns ns ns ns p=0.009 (large) ns ns ns p=0.371 p=0.668 (serine threonine) kinase; druggable genome no none NCOR2 Nuclear receptor corepressor 2 12q24.31 11% 22% 15% 0.3% <0.0001 18% 8% 0.106 ns ns ns ns ns ns ns ns p=0.009 (large) ns ns ns p=0.668 p=0.261 TF binding no none PKLR Pyruvate kinase, liver and RBC 1q22 12% 18% 15% 20.9% 0.0921 17% 7% 0.083 ns ns ns ns ns ns ns ns p=0.037 (large) ns ns ns p=0.733 p=0.340 kinase no FRUCTOSE-1,6-DIPHOSPHATE TRRAP Transformation/transcription domain associated protein 7q22.1 12% 20% 15% 0.9% <0.0001 18% 8% 0.106 ns ns ns ns ns ns ns ns p=0.009 (large) ns ns ns p=0.059 (poor; 10) p=0.247 (serine threonine) kinase; druggable genome; tumor suppressor; TF complex; histone modification; DNA repair; PI3 kinase no none WNT3A Wnt family member 3A 1q42.13 14% 13% 15% 24.9% 0.0086 18% 7% 0.053 ns ns ns ns ns ns ns ns p=0.037 (large) ns ns ns p=0.252 p=0.836 cell surface no none ABL2 ABL proto-oncogene 2, non-receptor tyrosine kinase 1q25.2 18% 4% 14% 22.0% 0.0320 15% 13% 0.771 ns ns ns ns ns ns ns p=0.003 (high) ns ns ns ns 0.634 p=0.580 (tyrosine) kinase, druggable genome no DASATINIB (tyrosine kinase inhibitor) CDK18 Cyclin dependent kinase 18 1q32.1 14% 11% 14% 28.2% 0.2337 18% 8% 0.106 ns ns ns ns ns ns ns ns ns ns ns ns p=0.561 p=0.258 (serine threonine) kinase; druggable genome; tumor suppressor no none CLTC clathrin heavy chain 17q23.1 15% 9% 14% 10.7% 0.2264 5% 25% 0.001 ns ns ns ns p=0.004 (neg) p=0.0003 pos) p=0.003 (high) ns ns ns ns ns 0.163 p=0.029 (poor; 10) no no none COMP Cartilage oligomeric matrix protein 19p13.11 11% 18% 14% 1.4% <0.0001 17% 8% 0.161 ns ns ns ns ns ns ns ns ns ns ns ns p=0.725 p=0.955 no no none EIF2B5 Eukaryotic translation initiation factor 2B subunit epsilon 3q27.1 14% 11% 14% 1.7% <0.0001 18% 8% 0.106 ns ns ns ns ns ns ns ns p=0.024 (large) ns p=0.039 (high) ns p=0.219 p=0.185 drug resistance no none ERCC4 ERCC excision repair 4, endonuclease catalytic subunit 16p13.12 19% 2% 14% 7.9% 0.0130 9% 20% 0.081 ns ns ns ns ns ns ns ns ns ns ns p=0.031 (no mut) 0.827 p=0.472 TF complex, TF binding, DNA repair yes none JMJD7-PLA2G4B JMJD7-PLA2G4B readthrough 15q15.1 10% 20% 14% 0.1% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns ns ns ns ns p=0.718 p=0.433 no no none JUP Junction plakoglobin 17q21.2 14% 11% 14% 2.5% <0.0001 18% 5% 0.022 ns ns ns ns ns ns ns ns ns ns ns ns p=0.910 p=0.127 no no none KDM2A Lysine demethylase 2A 11q13.2 15% 11% 14% 6.7% 0.0016 14% 15% 0.827 ns ns ns ns ns ns ns ns ns ns ns ns p=0.798 p=0.659 histone modification; DNA repair no DAMINOZIDE (histone demethylase inhibitor) LRP5 LDL receptor related protein 5 11q13.2 11% 20% 14% 6.5% 0.0010 15% 8% 0.238 ns ns ns ns ns ns ns ns ns ns ns ns p=0.722 p=0.203 tumor suppressor; transporter no none MAPK15 Mitogen-activated protein kinase 3 16p11.2 13% 13% 14% 18.4% 0.2135 12% 13% 0.838 ns p=0.041 (old) ns ns ns ns ns ns ns ns ns ns p=0.852 p=0.452 (serine threonine) kinase; druggable genome no none MAPK3 Mitogen-activated protein kinase 8 interacting protein 3 16p13.3 13% 13% 14% 7.5% 0.0069 17% 7% 0.083 ns ns ns ns ns ns ns ns ns ns ns ns p=0.548 p=0.576 (serine threonine) kinase; druggable genome; tumor suppressor no 5-IODOTUBERCIDIN; PURVALANOL (kinase inhibitors) MCM4 minichromosome maintenance complex component 4 8q11.21 16% 7% 14% 10.9% 0.2583 11% 18% 0.216 ns ns ns ns ns ns ns ns ns ns ns ns 0.791 p=0.901 no no none MUC1 mucin 1, cell surface associated 1q22 15% 9% 14% 21.2% 0.0509 15% 10% 0.386 ns ns ns ns ns ns ns ns ns ns p=0.039 (high) p=0.020 (mut) 0.957 p=0.776 tumor suppressor no none NFATC2 nuclear factor of activated T-cells 2 20q13.2 18% 4% 14% 6.7% 0.0016 12% 13% 0.838 ns ns ns ns p=0.036 (neg) ns ns ns ns ns ns ns 0.876 p=0.441 druggable genome, TF complex, TF binding, drug resistance no none PTPRR protein tyrosine phosphatase, receptor type R 12q15 16% 7% 14% 2.7% <0.0001 9% 20% 0.081 ns ns ns ns ns ns p=0.008 (high) ns ns ns ns p=0.037 (mut) 0.633 p=0.233 protein phosphatase, druggable genome no none PTPRT Protein tyrosine phosphatase, receptor type T 20q12-q13.11 14% 11% 14% 4.7% <0.0001 14% 13% 0.960 ns ns ns ns ns ns ns ns ns ns ns ns p=0.974 p=0.376 cell surface; protein phosphatase; druggable genome yes none PYGB Glycogen phosphorylase B 20p11.21 10% 20% 14% 1.8% <0.0001 17% 7% 0.083 ns ns ns ns ns ns ns ns ns ns ns ns p=0.575 p=0.581 druggable genome no none RASGRP4 RAS guanyl releasing protein 4 19q13.1 10% 20% 14% 1.0% <0.0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns p=0.571 p=0.548 no no none SETD1B SET domain containing 1B 12q24.31 11% 20% 14% 0.2% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns ns ns ns ns p=0.618 p=0.297 methyl transferase; histone modification no none SMC1A Structural maintenance of 1A Xp11.22 13% 13% 14% 0.4% <0.0001 18% 7% 0.053 ns ns ns p=0.037 (neg) ns ns ns ns ns ns ns ns p=0.813 p=0.599 tumor suppressor; DNA repair no none SYMPK Symplekin 19q13.32 10% 20% 14% 0.6% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns p=0.025 (large) ns ns ns p=0.344 p=0.704 no no none TPM3 tropomyosin 3 1q21.3 16% 7% 14% 20.4% 0.0791 15% 13% 0.771 ns ns ns ns ns ns ns p=0.034 (high) ns ns ns ns 0.803 p=0.551 no no none MED12L Mediator complex subunit 12 like 3q25.1 14% 13% 14% 1.8% <0.0001 12% 13% 0.838 ns ns ns ns ns ns ns ns ns ns ns ns p=0.647 p=0.376 TF binding no none CCNE2 cyclin E2 8q22.1 18% 2% 13% 18.6% 0.1262 9% 18% 0.129 p=0.0002 ns ns ns ns ns ns ns ns ns ns ns 0.162 p=0.586 tumor suppressor no none CDK12 cyclin dependent kinase 12 17q12 14% 9% 13% 9.9% 0.2110 11% 15% 0.459 ns ns ns ns ns ns ns ns ns ns ns ns 0.248 p=0.492 (serine threonine) kinase, druggable genome, tumor suppressor yes OLAPARIB (PARP inhibitor) DPP3 Dipeptidyl peptidase 3 11q13.2 11% 16% 13% 4.5% <0.0001 14% 10% 0.529 ns ns ns ns ns ns ns ns ns ns ns ns p=0.094 (better; 4) p=0.042 (better; 1) protease; druggable genome; neutral zinc metallopeptidase no none HK1 Hexokinase 1 10q22.1 10% 18% 13% 0.3% <0.0001 9% 12% 0.635 ns ns ns ns ns ns ns ns ns ns ns ns p=0.162 p=0.518 kinase no DB04395 (ATPase inhibitor) IGF1R insulin like growth factor 1 receptor 15q26.3 15% 9% 13% 2.7% <0.0001 11% 15% 0.459 ns ns ns ns ns ns ns ns ns ns ns ns 0.688 p=0.252 druggable genome, (tyrosine) kinase, tumor suppressor yes GEFITINIB (tyrosine kinase inhibitor); BMS-536924; LINSITINIB; BMS-754807; PICROPODOPHYLLIN (IGF1R inhibitors); AZD3463 (ALK inhibitor); DB04395 (ATPase inhibitor) ITGA3 integrin subunit alpha 3 17q21.33 14% 9% 13% 6.7% 0.0046 15% 8% 0.238 ns ns ns ns ns ns ns ns ns ns ns ns 0.052 (poor; 10) p=0.224 druggable genome, cell surface, drug resistance, external side of plasma membrane no none MAP3K10 Mitogen-activated protein kinase kinase kinase 10 19q13.2 10% 18% 13% 0.6% <0.0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns p=0.427 p=0.134 (serine threonine) kinase; druggable genome; TF binding no none MAP4K1 Mitogen-activated protein kinase kinase kinase kinase 1 19q13.1-q13.4 12% 16% 13% 0.9% <0.0001 17% 7% 0.083 ns ns ns ns ns ns ns ns p=0.025 (large) ns ns ns p=0.967 p=0.260 (serine threonine) kinase; druggable genome; tumor suppressor no none MAPKAPK2 Mitogen-activated protein kinase-activated protein kinase 2 1q32.1 13% 11% 13% 27.6% 0.0003 12% 15% 0.637 ns ns ns ns ns ns ns ns ns ns ns ns p=0.033 (poor; 10) p=0.130 (serine threonine) kinase; druggable genome no STAUROSPORINE; DB07406; DB07728; MK2A INHIBITOR (kinase inhibitors) MAST1 Microtubule associated serine/threonine kinase 1 19p13.2 10% 20% 13% 1.5% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns p=0.025 (large) ns ns ns p=0.215 p=0.751 (serine threonine) kinase; druggable genome no none MYT1 myelin transcription factor 1 20q13.33 15% 7% 13% 6.5% 0.0031 17% 8% 0.161 ns ns ns ns ns ns ns p=0.021 (low) ns ns ns ns 0.22 p=0.077 (better; 2) no no none PARP10 Poly(ADP-ribose) polymerase family member 10 8q24.3 12% 13% 13% 18.3% 0.1467 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns p=0.892 p=0.906 druggable genome no none PLCG1 gamma 1 20q12 14% 9% 13% 3.8% <0.0001 12% 10% 0.705 ns ns ns ns ns ns ns ns ns ns ns ns 0.868 p=0.583 phospholipase, lipase, druggable genome no none SGK3 serum/glucocorticoid regulated kinase family member 3 8q13.1 16% 4% 13% 14.0% 0.8221 8% 20% 0.041 p=0.023 ns ns ns p=0.036 (neg) p=0.008 (pos) p=0.017 (high) ns ns ns ns ns 0.36 p=0.730 (serine threonine) kinase, druggable genome no none SMARCA4 SWI/SNF related, matrix associated, dependent regulator of chromatin, subfamily a, member 4 19p13.2 10% 20% 13% 0.9% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns ns ns ns ns p=0.352 p=0.794 tumor suppressor; TF binding yes CISPLATINUM; VINORELBINE (chemotherapy drugs) SSH1 Slingshot protein phosphatase 1 12q24.11 11% 16% 13% 0.3% <0.0001 14% 10% 0.529 ns ns ns ns ns ns ns ns ns ns ns ns p=0.235 p=0.785 druggable genome; cell surface; protein phosphatase no none STAT3 signal transducer and activator of transcription 3 17q21.2 14% 9% 13% 1.6% <0.0001 15% 8% 0.238 ns ns ns p=0.032 (neg) ns ns ns ns ns ns ns ns 0.699 p=0.400 TF complex, TF binding, drug resistance, nuclear hormone receptor no ATIPRIMOD (STAT3 phosphorylation inhibitor); DCL000217 (STAT3 inhibitor) STAT5A Signal transducer and activator of transcription 5A 17q21.2 12% 13% 13% 1.6% <0.0001 20% 3% 0.005 ns ns ns ns ns ns ns ns ns ns ns ns p=0.717 p=0.380 tumor suppressor no none AR androgen receptor Xq12 13% 9% 13% 0.4% <0.0001 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns 0.983 p=0.394 druggable genome, nuclear hormone receptor, TF binding yes ABIRATERONE (CYP17 inhibitor); ENZALUTAMIDE; BICALUTAMIDE; FLUTAMIDE; NILUTAMIDE; CYPROTERONE (AR antagonists) etc BAI1 Adhesion G Protein-Coupled Receptor B1 (ADGRB1) 8q24.3 12% 11% 13% 0.0% <0.0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns p=1.000 p=0.136 G protein coupled receptor; druggable genome no none DIP2C Disco interacting protein 2 homolog C 10p15.3 11% 13% 13% 1.0% <0.0001 11% 10% 0.911 ns ns ns ns ns ns ns ns p=0.009 (large) ns ns ns p=0.948 p=0.499 TF binding no none E2F7 E2F transcription factor 7 12q21.2 13% 9% 13% 1.4% <0.0001 11% 15% 0.459 ns ns ns ns ns ns ns ns ns ns ns p=0.013 (mut) 0.047 (poor; 10) p=0.081 (poor; 8) tumor suppressor, TF complex no none FGF19 fibroblast growth factor 19 11q13.3 14% 9% 13% 19.2% 0.0924 11% 17% 0.320 ns ns ns ns ns ns p=0.018 (high) p=0.038 (high) ns ns ns ns 0.584 p=0.309 growth factor yes none FGF3 Fibroblast growth factor 3 11q13.3 13% 13% 13% 18.5% 0.1327 9% 17% 0.202 ns ns ns ns ns ns p=0.040 (high) ns ns ns ns ns p=0.407 p=0.186 growth factor yes none INSR Insulin receptor 19p13.2 11% 18% 13% 0.6% <0.0001 17% 5% 0.037 ns ns ns ns ns ns ns ns ns ns ns ns p=0.584 p=0.464 (tyrosine) kinase; druggable genome; tumor suppressor yes INSULIN; NOVORAPID; GLARGINE; VELOSULIN; CHEMBL2104391 (insulin); DB08513; DB03909; LINSITINIB (IGF1R inhibitor) ITGA2B Integrin subunit alpha 2b 17q21.31 11% 13% 13% 0.9% <0.0001 18% 3% 0.008 ns ns ns ns ns ns ns ns p=0.039 (large) ns ns ns p=0.389 p=0.619 druggable genome; cell surface; external side of plasma membrane no TIROFIBAN; EPTIFIBATIDE; LEFRADAFIBAN; GANTOFIBAN (platelet aggregation inhibitors) L3MBTL1 l(3)mbt-like 1 (Drosophila) 20q13.12 12% 11% 13% 4.4% <0.0001 17% 7% 0.083 ns ns ns ns ns ns ns ns ns ns ns ns p=0.657 p=0.394 tumor suppressor no 2-(N-MORPHOLINO)-ETHANESULFONIC ACID MDM2 MDM2 proto-oncogene 12q15 14% 7% 13% 3.7% <0.0001 6% 18% 0.034 ns ns ns ns p=0.004 (neg) ns p=0.040 (high) ns ns ns ns p=0.004 (mut) p=0.068 (poor; 11) p=0.007 (poor; 10) druggable genome, tumor suppressor yes CISPLATINUM; PEMETREXED (chemotherapy drugs); DB02872 (MDM2 inhibitor) MFSD4 Major Facilitator Superfamily Domain Containing 4A 1q32.1 13% 9% 13% 28.2% 0.0001 15% 8% 0.238 ns ns ns ns ns ns ns ns ns ns ns p=0.028 (mut) 0.929 p=0.422 druggable genome no none MKS1 Meckel syndrome, type 1 17q22 14% 9% 13% 8.9% 0.1545 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns 0.478 p=0.962 no no none NCSTN Nicastrin 1q23.2 12% 13% 13% 21.4% 0.0156 14% 10% 0.529 ns ns ns ns ns ns ns ns ns ns ns ns p=0.072 (poor; 12) p=0.392 protease no none NTHL1 nth like DNA glycosylase 1 16p13.3 14% 7% 13% 9.4% 0.2283 14% 10% 0.529 ns ns ns ns ns ns ns ns ns p=0.015 (neg) p=0.008 (high) ns 0.448 p=0.137 DNA repair no none PIK3R2 Phosphoinositide-3-kinase regulatory subunit 2 19p13.11 10% 16% 13% 1.5% <0.0001 15% 5% 0.061 ns ns ns ns ns ns ns ns ns ns ns ns p=0.567 p=0.632 (PI3) kinase; druggable genome yes PKI-587; SF1126; GDC-0941; GDC-0980; GSK2126458; GSK2636771; PI-103; QUERCETIN; XL147 (kinase inhibitors) PKD1 Polycystin 1, transient receptor potential channel interacting 16p13.3 12% 11% 13% 9.4% 0.2283 14% 10% 0.529 ns ns ns ns ns ns ns ns ns ns ns ns p=0.874 p=0.470 cell surface; tumor suppressor; transporter; ion channel no none SETDB1 SET domain bifurcated 1 1q21.3 15% 4% 13% 18.6% 0.0830 17% 8% 0.161 ns ns ns ns ns ns ns ns ns ns ns p=0.035 (mut) 0.288 p=0.071 (poor; 7) methyl transferase, histone modification no none SH2D2A SH2 domain containing 2A 1q23.1 11% 13% 13% 20.8% 0.0229 14% 8% 0.344 ns ns ns ns ns ns ns ns p=0.039 (large) ns ns ns p=0.667 p=0.257 no no none SMO Smoothened, frizzled class receptor 7q32.1 10% 16% 13% 0.8% <0.0001 15% 7% 0.130 ns ns ns ns ns ns ns ns ns ns ns ns p=0.861 p=0.267 G protein coupled receptor; druggable genome yes VISMODEGIB; ERISMODEGIB; BMS-833923; TALADEGIB (Hedgehog/Smoothened inhibitors) TAOK2 TAO kinase 2 16p11.2 13% 9% 13% 7.5% 0.0357 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns 0.566 p=0.696 (serine threonine) kinase, druggable genome, tumor suppressor no none UCK2 uridine-cytidine kinase 2 1q24.1 13% 9% 13% 22.8% 0.0061 17% 8% 0.161 ns ns ns ns ns ns ns ns ns ns ns ns 0.028 (poor; 11) p=0.314 kinase no DB02097; URIDINE 5'-TRIPHOSPHATE; CITRIC ACID VEGFA vascular endothelial growth factor A 6p21.1 11% 13% 13% 0.5% <0.0001 9% 12% 0.635 ns ns ns ns ns ns ns ns ns ns ns ns p=0.542 p=0.821 cell surface; growth factor no none VPS16 VPS16, CORVET/HOPS core subunit 20p13 13% 9% 13% 1.8% <0.0001 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns p=0.035 (mut) 0.587 p=0.317 no no none WNT3 Wnt family member 3 17q21.31-q21.32 11% 13% 13% 1.6% <0.0001 18% 3% 0.008 ns ns ns ns ns ns ns ns ns ns p=0.023 (high) ns p=0.538 p=0.656 no no none ZNF217 zinc finger protein 217 20q13.2 15% 4% 13% 9.2% 0.1967 6% 20% 0.019 ns ns ns ns p=0.004 (neg) ns ns ns ns ns ns p=0.009 (mut) 0.978 p=0.922 no yes none AXIN1 Axin 1 16p13.3 11% 11% 12% 10.0% 0.4841 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns p=0.710 p=0.167 no yes none AXIN2 axin 2 17q24.1 14% 7% 12% 7.7% 0.0859 12% 12% 0.937 ns ns ns ns ns ns p=0.020 (high) ns ns ns ns ns 0.598 p=0.631 tumor suppressor yes none ERBB4 erb-b2 receptor tyrosine kinase 4 2q34 13% 7% 12% 0.3% <0,0001 11% 13% 0.637 ns ns ns ns ns ns ns ns ns ns ns ns 0.418 p=0.651 (tyrosine) kinase, druggable genome yes NERATINIB; LAPATINIB; PELITINIB; BMS-599626; DACOMITINIB; AFATINIB DIMALEATE; GEFITINIB; POZIOTINIB (tyrosine kinase inhibitors) EXOC7 exocyst complex component 7 17q25.1 13% 7% 12% 5.0% 0.0008 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns 0.762 p=0.973 methyl transferase, histone modification no none EZH1 enhancer of zeste 1 polycomb repressive complex 2 subunit 17q21.2 12% 9% 12% 1.2% <0,0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns 0.353 p=0.722 no no none LAMA1 Laminin subunit alpha 1 18p11.31 10% 13% 12% 0.5% <0,0001 15% 7% 0.130 ns ns ns ns ns ns ns ns ns ns ns ns p=0.424 p=0.192 no no none MAPT Microtubule associated protein tau 17q21.31 11% 11% 12% 1.3% <0,0001 11% 8% 0.664 ns ns ns ns ns ns ns ns p=0.015 (large) ns ns ns p=0.116 p=0.934 no no none MED12 Mediator complex subunit 12 Xq13.1 11% 11% 12% 0.3% <0,0001 17% 7% 0.083 ns ns ns ns ns ns ns ns ns ns ns ns p=0.250 p=0.117 TF binding yes none MYLK2 myosin light chain kinase 2 20q11.21 12% 9% 12% 1.7% <0,0001 12% 10% 0.705 ns ns ns ns ns ns ns ns ns ns ns ns 0.706 p=0.411 (serine threonine) kinase, druggable genome no PRENYLAMINE (calcium channel blocker) MYLK3 Myosin light chain kinase 3 16q11.2 11% 11% 12% 1.7% <0,0001 9% 8% 0.880 ns ns ns ns ns ns ns ns ns ns ns ns p=0.765 p=0.350 (serine threonine) kinase; druggable genome no none NPR2 Natriuretic peptide receptor 2 9p13.3 10% 13% 12% 0.8% <0,0001 14% 5% 0.099 ns ns ns ns ns ns ns ns ns ns ns ns p=0.644 p=0.330 druggable genome; kinase; tumor suppressor no ERYTHRITYL TETRANITRATE; 124584-08-3; NPPC (vasodilator agents) NRBP2 Nuclear receptor binding protein 2 8q24.3 10% 13% 12% 18.4% 0.0590 9% 12% 0.635 ns ns ns ns ns ns ns ns ns ns ns ns p=0.874 p=0.875 (serine threonine) kinase; druggable genome no none NUAK2 NUAK family kinase 2 1q32.1 13% 7% 12% 28.0% 0.0001 12% 12% 0.937 ns ns ns ns ns ns ns ns ns ns ns ns 0.493 p=0.902 (serine threonine) kinase, druggable genome no none PAK1 p21 (RAC1) activated kinase 1 11q13.5-q14.1 13% 7% 12% 10.2% 0.5345 9% 15% 0.306 ns ns ns ns ns ns p=0.040 (high) ns ns ns ns p=0.028 (mut) 0.003 (poor; 11) p=0.021 (poor; 9) (serine threonine) kinase, druggable genome, tumor suppressor yes none PHKG1 Phosphorylase kinase catalytic subunit gamma 1 7p11.2 10% 16% 12% 1.0% <0,0001 15% 5% 0.061 ns ns ns ns ns ns ns ns ns ns ns ns p=0.795 p=0.252 (serine threonine) kinase; druggable genome no none PRKCB beta 16p12.2-p12.1 11% 11% 12% 7.5% 0.0690 14% 10% 0.529 ns ns ns ns ns ns ns ns ns ns ns ns p=0.982 p=0.327 (serine threonine) kinase; druggable genome; histone modification no ENZASTAURIN; RUBOXISTAURIN; BRYOSTATIN; PKCBETA INHIBITOR (PKC inhibitors); INGENOL MEBUTATE (PKC activator) etc PTPRA Protein tyrosine phosphatase, receptor type A 20p13 10% 13% 12% 1.7% <0,0001 11% 12% 0.850 ns ns ns ns ns ns ns ns p=0.024 (large) ns ns ns p=0.788 p=0.639 protein phosphatase; druggable genome no none RBBP5 RB binding protein 5, histone lysine methyltransferase complex subunit 1q32.1 13% 7% 12% 28.1% <0,0001 14% 12% 0.740 ns ns ns ns ns ns p=0.018 (high) ns ns ns ns ns 0.572 p=0.867 histone modification no none SMURF1 SMAD specific E3 ubiquitin protein ligase 1 7q22.1 11% 11% 12% 0.9% <0,0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns p=0.506 p=0.712 no no none SRC SRC proto-oncogene, non-receptor tyrosine kinase 20q11.23 11% 11% 12% 2.9% <0,0001 11% 12% 0.850 ns ns ns ns ns p=0.005 (pos) ns ns ns ns ns ns p=0.983 p=0.345 tyrosine kinase; druggable genome; tumor suppressor yes DASATINIB; BOSUTINIB; VANDETANIB; MASITINIB; PONATINIB; SARACATINIB; KX2-391 (tyrosine kinase inhibitors); GSK-3 INHIBITOR XIII etc. TCF7L2 Transcription factor 7 like 2 10q25.2-q25.3 11% 11% 12% 0.2% <0,0001 14% 8% 0.344 ns ns ns ns ns ns ns ns ns ns ns ns p=0.805 p=0.372 tumor suppressor;TF complex; TF binding no none ADCK2 AarF domain containing kinase 2 7q34 10% 11% 11% 1.0% <0,0001 15% 5% 0.061 ns ns ns ns ns ns ns ns ns ns ns ns p=0.335 p=0.946 (serine threonine) kinase; druggable genome no none CLIP1 CAP-Gly domain containing linker protein 1 12q24.31 11% 9% 11% 0.2% <0,0001 14% 5% 0.099 ns ns ns ns ns ns ns ns ns ns ns ns 0.198 p=0.998 no no none FARP1 FERM, ARH/RhoGEF and pleckstrin domain protein 1 13q32.2 11% 9% 11% 1.4% <0,0001 8% 12% 0.435 ns ns ns ns ns ns ns ns ns ns ns ns 0.307 p=0.496 no no none FN1 fibronectin 1 2q35 11% 9% 11% 0.3% <0,0001 5% 17% 0.025 ns ns ns ns ns ns ns p=0.011 (high) ns p=0.045 (pos) ns ns 0.827 p=0.738 no no none IRAK1 interleukin 1 receptor associated kinase 1 Xq28 11% 9% 11% 1.0% <0,0001 15% 7% 0.130 ns ns ns ns ns ns ns ns ns ns ns ns 0.347 p=0.071 (better; 1) (serine threonine) kinase, druggable genome no IRAK-1/4 INHIBITOR KDM8 lysine demethylase 8 16p12.1 11% 9% 11% 7.8% 0.1778 12% 8% 0.485 ns ns ns ns ns ns ns ns ns ns ns ns 0.776 p=0.509 histone modification no none PI4KB phosphatidylinositol 4-kinase beta 1q21.3 11% 9% 11% 18.3% 0.0359 15% 5% 0.061 ns ns ns ns ns ns ns ns ns ns ns ns 0.364 p=0.898 druggable genome, (PI3) kinase no PIK-93 (PI3/PI4 kinase inhibitor); WORTMANNIN (PI3 kinase inhibitor) PIP4K2B phosphatidylinositol-5-phosphate 4-kinase type 2 beta 17q12 11% 9% 11% 6.3% 0.0327 11% 10% 0.911 ns ns ns ns ns ns ns ns ns ns ns ns 0.447 p=0.405 kinase no none PIP5K1A phosphatidylinositol-4-phosphate 5-kinase type 1 alpha 1q21.3 11% 9% 11% 18.3% 0.0359 11% 12% 0.850 ns ns ns ns ns ns ns p=0.011 (high) ns ns ns ns 0.772 p=0.892 kinase no none SERPINE1 serpin family E member 1 7q22.1 12% 7% 11% 0.5% <0.0001 14% 7% 0.199 ns p=0.020 (old) ns ns ns ns ns ns ns ns ns ns 0.678 p=0.924 protease inhibitor, druggable genome no TROGLITAZONE (PPAR activator) CASP2 2 7q34 10% 9% 10% 1.2% <0.0001 9% 12% 0.635 ns ns ns ns ns ns ns ns ns ns ns ns 0.354 p=0.875 protease, tumor suppressor, druggable genome no Z-VDVAD-FMK (CASP2 inhibitor) FGF4 Fibroblast growth factor 4 11q13.3 10% 11% 10% 18.6% 0.0174 6% 13% 0.165 ns ns ns ns ns ns ns p=0.03 (high) ns ns ns ns p=0.073 (poor; 7) p=0.101 growth factor yes PENTOSAN POLYSULFATE (FGF inhibitor) KIF3B kinesin family member 3B 20q11.21 10% 9% 10% 1.7% <0.0001 8% 12% 0.435 ns ns ns ns ns ns ns ns ns ns ns ns 0.068 (poor; 7) p=0.099 (poor; 6) tumor suppressor no none MMP9 matrix metallopeptidase 9 20q13.12 10% 9% 10% 4.5% 0.0026 12% 8% 0.485 ns ns ns ns ns ns ns ns ns ns p=0.049 (high) ns 0.563 p=0.928 protease, neutral zinc metallopeptidase, druggable genome no MARIMASTAT; DCL000927 (MMP inhibitors); NIFEDIPINE (calcium channel blocker); METHYLDOPA (dopa decarboxylase inhibitor) NSD1 nuclear receptor binding SET domain protein 1 5q35.3 12% 7% 10% 1.1% <0.0001 11% 8% 0.664 ns ns ns ns ns ns ns ns ns ns ns p=0.004 (mut) 0.748 p=0.976 methyl transferase, histone modification, TF binding yes none PDK2 pyruvate dehydrogenase kinase 2 17q21.33 10% 9% 10% 6.6% 0.0956 9% 7% 0.747 ns ns ns ns ns ns ns ns p=0.039 (large) ns ns ns 0.035 (poor; 10) p=0.245 (serine threonine) kinase, druggable genome no CPI-613; DB08610 (mitochondrial metabolism inhibitors) PAK3 p21 (RAC1) activated kinase 3 Xq23 12% 7% 10% 0.3% <0.0001 8% 12% 0.435 ns ns ns ns ns ns ns p=0.022 (high) ns ns ns ns 0.058 (better; 3) p=0.201 (serine threonine) kinase, druggable genome, tumor suppressor yes none

* cBioportal METABRIC + Nature 2012 + Nature 2016; ER positive (by IHC) FBC with CNA data; n=1498 ** p-value corrected for multiple comparisons (Bonferroni); bold are significant; calculated at https://www.medcalc.org/calc/comparison_of_proportions.php *** significant associations are shown in bold; trends or significant associations with <5 uncensored events are shown in italic; for each association, the p-value, direction of association, and the number of uncensored events are indicated # based on The Drug Interaction Database (http://dgidb.genome.wustl.edu/); categories are groups of genes considered by some to be potentially druggable targets ## based on The Drug Interaction Database (http://dgidb.genome.wustl.edu/); as reported by: BaderLabGenes, CarisMolecularIntelligence, FoundationOneGenes, GO, GuideToPharmacologyGenes, HopkinsGroom, MskImpact, RussLampel, and dGene ### based on The Drug Interaction Database (http://dgidb.genome.wustl.edu/); from 15 source databases (CIVIC, CancerCommons; ChEMBL, ClearityFoundationBiomarkers, ClearityFoundationClinicalTrial, DoCM, DrugBank, GuideToPharmacologyInteractions, MyCancerGenome, MyCancerGenomeClinicalTrial, PharmGKB, TALC, TEND, TTD, TdgClinicalTrial)

Abbreviations: FFPE = formalin-fixed paraffin embedded; FF = fresh frozen; NA = not assesse; MBC = male breast cancer; FBC = female breast cancer; TF = transcription factor; KM=kaplan meier; OS=overall survival; 5Y=5-year

Please cite: Wagner AH, Coffman AC, Ainscough BJ, Spies NC, Skidmore ZL, Campbell KM, Krysiak K, Pan D, McMichael JF, Eldred JM, Walker JR, Wilson RK, Mardis ER, Griffith M, Griffith OL. DGIdb 2.0: mining clinically relevant drug-gene interactions. Nucleic Acids Research. 2016 Jan 4;44(D1):D1036-44. doi:10.1093/nar/gkv1165