Supplementary Table 1. List of up-regulated in abiraterone-resistant VCaP xenograft samples PIK3IP1 phosphoinositide-3-kinase interacting 1 TMEM45A transmembrane protein 45A THBS1 thrombospondin 1 C7orf63 7 open reading frame 63 OPTN optineurin FAM49A family with sequence similarity 49, member A APOL4 apolipoprotein L, 4 C17orf108|LOC201229 chromosome 17 open reading frame 108 | hypothetical protein LOC201229 SNORD94 small nucleolar RNA, C/D box 94 PCDHB11 protocadherin beta 11 RBM11 RNA binding motif protein 11 C6orf225 chromosome 6 open reading frame 225 KIAA1984|C9orf86|TMEM14 1 KIAA1984 | chromosome 9 open reading frame 86 | transmembrane protein 141 KIAA1107 TLR3 toll-like receptor 3 LPAR6 lysophosphatidic acid receptor 6 KIAA1683 GRB10 growth factor receptor-bound protein 10 TIMP2 TIMP metallopeptidase inhibitor 2 CCDC28A coiled-coil domain containing 28A FBXL2 F-box and leucine-rich repeat protein 2 NOV nephroblastoma overexpressed TSPAN31 31 NR3C2 nuclear receptor subfamily 3, group C, member 2 DYNC2LI1 dynein, cytoplasmic 2, light intermediate chain 1 C15orf51 dynamin 1 SAMD13 sterile alpha motif domain containing 13 RASSF6 Ras association (RalGDS/AF-6) domain family member 6 ZNF167 protein 167 GATA2 GATA binding protein 2 NUDT7 nudix (nucleoside diphosphate linked moiety X)-type motif 7 DNAJC18 DnaJ (Hsp40) homolog, subfamily C, member 18 SNORA57 small nucleolar RNA, H/ACA box 57 CALCOCO1 calcium binding and coiled-coil domain 1 RLN2 relaxin 2 ING4 inhibitor of growth family, member 4 NMT2 N-myristoyltransferase 2 ZNF512 zinc finger protein 512 YPEL5 yippee-like 5 (Drosophila) ANKRD31 ankyrin repeat domain 31 CSTT cystatin pseudogene EFCAB7 EF-hand calcium binding domain 7 FAM160A1 family with sequence similarity 160, member A1 PPM1N|FLJ40125 protein phosphatase, Mg2+/Mn2+ dependent, 1N (putative) | protein phosphatase 1B-like DENND5A DENN/MADD domain containing 5A RG9MTD3 RNA (guanine-9-) domain containing 3 SNORD104 small nucleolar RNA, C/D box 104 C20orf194 chromosome 20 open reading frame 194 PNRC1 proline-rich nuclear receptor coactivator 1 THSD1P1 thrombospondin, type I, domain containing 1 pseudogene 1 SGCB sarcoglycan, beta (43kDa -associated glycoprotein) TMC5 transmembrane channel-like 5 ZNF10|ZNF268 zinc finger protein 10 | zinc finger protein 268 ARHGEF37|FLJ41603 Rho guanine nucleotide exchange factor (GEF) 37 | FLJ41603 protein KIDINS220 kinase D-interacting substrate, 220kDa BTG2 BTG family, member 2 LPIN1 lipin 1 PDZD4 PDZ domain containing 4 FCHSD1|RELL2 FCH and double SH3 domains 1 | RELT-like 2 DENND5B DENN/MADD domain containing 5B AMN1|C12orf72 antagonist of mitotic exit network 1 homolog (S. cerevisiae) | open reading frame 72 ANKZF1 ankyrin repeat and zinc finger domain containing 1 RMND1 required for meiotic nuclear division 1 homolog (S. cerevisiae) FAM154B family with sequence similarity 154, member B C1orf61 open reading frame 61 ATXN1 ataxin 1 SERPINA3 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 TBC1D19 TBC1 domain family, member 19 KLHL5 kelch-like 5 (Drosophila) thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) | THRA|NR1D1 nuclear receptor subfamily 1, group D, member 1 H3F3B H3 , family 3B (H3.3B) NAALADL2 N-acetylated alpha-linked acidic dipeptidase-like 2 BTN2A2 butyrophilin, subfamily 2, member A2 CA13 carbonic anhydrase XIII FAM124A family with sequence similarity 124A C7orf41 open reading frame 41 ATP6V1H ATPase, H+ transporting, lysosomal 50/57kDa, V1 subunit H CCL28 chemokine (C-C motif) ligand 28 C21orf57 chromosome 21 open reading frame 57 ZNF550 zinc finger protein 550 RASA4|RASA4P|RASA4B|P RAS p21 protein activator 4 | RAS p21 protein activator 4 pseudogene | RAS p21 protein activator OLR2J4|LOC100132214|LO 4B | polymerase (RNA) II (DNA directed) polypeptide J4, pseudogene | similar to calcium-promoted C100286937 Ras inactivator | similar to HSPC047 protein SPATA7 spermatogenesis associated 7 BCAS3 breast carcinoma amplified sequence 3 CASP8 caspase 8, apoptosis-related peptidase LCP1 lymphocyte cytosolic protein 1 (L-plastin) MMP26 matrix metallopeptidase 26 PAN2 PARP16 poly (ADP-ribose) polymerase family, member 16 GNB5 guanine nucleotide binding protein (G protein), beta 5 MYT1 transcription factor 1 SLC12A6 solute carrier family 12 (potassium/chloride transporters), member 6 MEAF6 MYST/Esa1-associated factor 6 GPRC5B G protein-coupled receptor, family C, group 5, member B radial spoke head 10 homolog B (Chlamydomonas) | radial spoke head 10 homolog B2 RSPH10B|RSPH10B2 (Chlamydomonas) MCTS1 malignant T cell amplified sequence 1 RAS p21 protein activator 4 | RAS p21 protein activator 4 pseudogene | RAS p21 protein activator RASA4|RASA4P|RASA4B|P 4B | polymerase (RNA) II (DNA directed) polypeptide J4, pseudogene | similar to calcium-promoted OLR2J4|LOC100132214 Ras inactivator CD207 (MARCH8) membrane-associated ring finger (C3HC4) 8 RGL3 ral guanine nucleotide dissociation stimulator-like 3 radial spoke head 10 homolog B (Chlamydomonas) | radial spoke head 10 homolog B2 RSPH10B|RSPH10B2 (Chlamydomonas) SLC38A3 solute carrier family 38, member 3 SCN4B sodium channel, voltage-gated, type IV, beta C3orf17 open reading frame 17 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 SMYD2 SET and MYND domain containing 2 pleckstrin homology domain containing, family M (with RUN domain) member 1 pseudogene | similar PLEKHM1P|LOC100291232 to hCG2002091 C5orf32 open reading frame 32 GPM6B glycoprotein M6B B9D1 B9 1 PHKA2 phosphorylase kinase, alpha 2 (liver) OR1J2 olfactory receptor, family 1, subfamily J, member 2 NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 SYNGR1 synaptogyrin 1 METTL6 methyltransferase like 6 OR56A4 olfactory receptor, family 56, subfamily A, member 4 ROPN1L ropporin 1-like APPL2 adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2 HSF2 heat shock transcription factor 2 RNF145 ring finger protein 145 NPHP1 nephronophthisis 1 (juvenile) complement component 4A (Rodgers blood group) | complement component 4B (Chido blood group) C4A|C4B|LOC100292046|L | similar to Complement component 4A (Rodgers blood group) | similar to complement component OC100294156 4A (Rodgers blood group) complement component 4A (Rodgers blood group) | complement component 4B (Chido blood group) C4A|C4B|LOC100292046|L | similar to Complement component 4A (Rodgers blood group) | similar to complement component OC100294156 4A (Rodgers blood group) CYP4F22 cytochrome P450, family 4, subfamily F, polypeptide 22 KIAA1704 PJA2 praja ring finger 2 C20orf90 chromosome 20 open reading frame 90 TMF1 TATA element modulatory factor 1 NEUROD4 neurogenic differentiation 4 SNX13 sorting nexin 13 DNAH12 dynein, axonemal, heavy chain 12 SEPSECS Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase C12orf76 chromosome 12 open reading frame 76 C3orf19|TMEM135 chromosome 3 open reading frame 19 | transmembrane protein 135 GJA5 gap junction protein, alpha 5, 40kDa SKP1 S-phase kinase-associated protein 1 RAB3GAP2 RAB3 GTPase activating protein subunit 2 (non-catalytic) HEMK1|C3orf18 HemK methyltransferase family member 1 | chromosome 3 open reading frame 18 RPS4Y1 ribosomal protein S4, Y-linked 1 ASB3|LOC100302652|GPR7 5 ankyrin repeat and SOCS box-containing 3 | GPR75-ASB3 | G protein-coupled receptor 75 CTBS chitobiase, di-N-acetyl- MLLT3 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3 KCNIP2 Kv channel interacting protein 2 golgi-associated PDZ and coiled-coil motif containing | golgi associated PDZ and coiled-coil motif containing | discoidin, CUB and LCCL domain containing 1 | c-ros oncogene 1 , receptor tyrosine GOPC|DCBLD1|ROS1 kinase CCDC65 coiled-coil domain containing 65 VPS8 vacuolar protein sorting 8 homolog (S. cerevisiae) PHF21A PHD finger protein 21A OR5B2 olfactory receptor, family 5, subfamily B, member 2 FBXO24 F-box protein 24 NBR1 neighbor of BRCA1 gene 1 IL1F8 interleukin 1 family, member 8 (eta) NBAS neuroblastoma amplified sequence ZNF148 zinc finger protein 148 MIR206 microRNA 206 ARG1 arginase, liver TM4SF4 transmembrane 4 L six family member 4 RELB v-rel reticuloendotheliosis viral oncogene homolog B SH2D1B SH2 domain containing 1B DCP1B DCP1 decapping homolog B (S. cerevisiae) WDR33 WD repeat domain 33 MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2 SLC5A12 solute carrier family 5 (sodium/ cotransporter), member 12

Supplementary Table 2. List of genes down-regulated in abiraterone-resistant VCaP xenograft samples

DPP4 dipeptidyl-peptidase 4 FAM189A2 family with sequence similarity 189, member A2 CENPE centromere protein E, 312kDa SGK3|C8orf44 serum/glucocorticoid regulated kinase family, member 3 | chromosome 8 open reading frame 44 OAS3 2'-5'-oligoadenylate synthetase 3, 100kDa MKI67 antigen identified by monoclonal antibody Ki-67 C15orf42 chromosome 15 open reading frame 42 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila) CDK1|CDC2 cyclin-dependent kinase 1 | cell division cycle 2, G1 to S and G2 to M NCAPG|LCORL non-SMC condensin I complex, subunit G | ligand dependent nuclear receptor corepressor-like LOC1720 dihydrofolate reductase pseudogene ARHGAP11A Rho GTPase activating protein 11A SHCBP1 SHC SH2-domain binding protein 1 NDC80 ECT2 epithelial cell transforming sequence 2 oncogene KIF18B kinesin family member 18B KIAA0101|CSNK1G1 KIAA0101 | casein kinase 1, gamma 1 H2AFZ H2A histone family, member Z TYMS thymidylate synthetase KIAA1524 KIF11 kinesin family member 11 NUF2 DHFR dihydrofolate reductase RTKN2 rhotekin 2 OAS2 2'-5'-oligoadenylate synthetase 2, 69/71kDa NCAPG2 non-SMC condensin II complex, subunit G2 E2F1 E2F transcription factor 1 MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast) CNKSR2 connector enhancer of kinase suppressor of Ras 2 HIST1H4I histone cluster 1, H4i DIAPH3 diaphanous homolog 3 (Drosophila) TOP2A topoisomerase (DNA) II alpha 170kDa BRIP1 BRCA1 interacting protein C-terminal helicase 1 GINS2 GINS complex subunit 2 (Psf2 homolog) TMPO thymopoietin GCLM glutamate-cysteine ligase, modifier subunit SMC4 structural maintenance of 4 FANCI|POLG Fanconi anemia, complementation group I | polymerase (DNA directed), gamma CALY calcyon neuron-specific vesicular protein HES6 hairy and enhancer of split 6 (Drosophila) SPIN4 spindlin family, member 4 FBXO5 F-box protein 5 FANCA|ZNF276 Fanconi anemia, complementation group A | zinc finger protein 276 CXorf27 chromosome X open reading frame 27 DGKE diacylglycerol kinase, epsilon 64kDa TAL1 T-cell acute lymphocytic leukemia 1 PARP12 poly (ADP-ribose) polymerase family, member 12 LRRC59 leucine rich repeat containing 59 SETD8 SET domain containing ( methyltransferase) 8 SLC25A30 solute carrier family 25, member 30 B4GALT6 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 6 MASTL microtubule associated serine/threonine kinase-like MFAP4 microfibrillar-associated protein 4 FRMD7 FERM domain containing 7 CD109 DLK1 delta-like 1 homolog (Drosophila) COMTD1 catechol-O-methyltransferase domain containing 1 LOC375196 ZNF765|ZNF761|ZNF813|ZNF zinc finger protein 765 | zinc finger protein 761 | zinc finger protein 813 | zinc finger protein 845 | 845|ZNF701 zinc finger protein 701 MIR223 microRNA 223 ABCG8 ATP-binding cassette, sub-family G (WHITE), member 8 GATA6 GATA binding protein 6 OAF RIMBP3|RIMBP3B|RIMBP3C RIMS binding protein 3 | RIMS binding protein 3B | RIMS binding protein 3C IPO11 importin 11 LOC388955 PX19 protein pseudogene NCRNA00236 non-protein coding RNA 236 ERVWE1 endogenous retroviral family W, env(C7), member 1 CST8 cystatin 8 (cystatin-related epididymal specific) MMP14 matrix metallopeptidase 14 (membrane-inserted) OSBPL3 oxysterol binding protein-like 3 RAX2 retina and anterior neural fold homeobox 2 SPIRE1 spire homolog 1 (Drosophila) HNRNPCL1|LOC649330 heterogeneous nuclear ribonucleoprotein C-like 1 HIPK2 homeodomain interacting protein kinase 2 IFITM5 interferon induced transmembrane protein 5 ADCY8 adenylate cyclase 8 (brain) OLIG2 oligodendrocyte lineage transcription factor 2 CSPG5 chondroitin sulfate proteoglycan 5 (neuroglycan C) PSMB10|CTRL proteasome (prosome, macropain) subunit, beta type, 10 | chymotrypsin-like UCK1 uridine-cytidine kinase 1 G2E3 G2/M-phase specific E3 ligase ZNF615|ZNF432 zinc finger protein 615 | zinc finger protein 432 GFI1 growth factor independent 1 transcription repressor CHCHD3 coiled-coil-helix-coiled-coil-helix domain containing 3 PID1 phosphotyrosine interaction domain containing 1 DPF1 D4, zinc and double PHD fingers family 1 LOC400965 FCGR3A|FCGR3B|LOC100292 Fc fragment of IgG, low affinity IIIa, receptor (CD16a) | Fc fragment of IgG, low affinity IIIb, 420 receptor (CD16b) | similar to hCG2039165 KANK2 KN motif and ankyrin repeat domains 2 CORO1A coronin, actin binding protein, 1A HKDC1 domain containing 1 SLC18A2 solute carrier family 18 (vesicular monoamine), member 2 ZFP91-CNTF TJP1 tight junction protein 1 (zona occludens 1) TMTC3 transmembrane and tetratricopeptide repeat containing 3 RC3H2 ring finger and CCCH-type zinc finger domains 2 DIO3 deiodinase, iodothyronine, type III CHPT1 choline phosphotransferase 1 SHISA7|hCG_2039146 shisa homolog 7 (Xenopus laevis) | UPF0626 protein A PRSS55|UNQ9391 protease, serine, 55 | tryptophan/serine protease MEI1 meiosis inhibitor 1 EPYC epiphycan SRRM1 serine/arginine repetitive matrix 1 ARHGAP30 Rho GTPase activating protein 30 CXorf41 chromosome X open reading frame 41 TAS2R8 taste receptor, type 2, member 8 MYOZ1 myozenin 1 PURA purine-rich element binding protein A FAM150A family with sequence similarity 150, member A SFRS15 splicing factor, arginine/serine-rich 15 CAV3 caveolin 3 PDCL2 phosducin-like 2 IPO7 importin 7 SCRT1 scratch homolog 1, zinc finger protein (Drosophila) FAM170A family with sequence similarity 170, member A KLK6 kallikrein-related peptidase 6 FMO3 flavin containing monooxygenase 3 WDR72 WD repeat domain 72

Supplementary Table 3. AR mutation detected in RNA-Seq analysis

Pred. Ref. Alt. Allele Ref. Alt. Allele Chr Position Ref Alt ID ID P * Change Depth Depth Freq. Depth Depth Freq. chrX 66765585 G T Q199H 1-1 119 2 1.65% 1-2 23 2 8.00% 0.1359 chrX 66765942 A T K318N 1-1 227 23 7.88% 1-2 27 12 27.91% 0.0006 chrX 66937442 G A A766T 1-1 365 32 7.90% 1-2 48 5 9.26% 0.7888 chrX 66943607 T C M896T 1-1 306 15 4.41% 1-2 60 3 4.76% 1.0000 chrX 66937442 G A A766T 3-1 29 2 6.06% 3-2 72 11 12.94% 0.5090 chrX 66765943 G A G319R 7-1 1555 57 3.52% 7-2 1469 44 2.88% 0.3626 chrX 66766087 T C F367L 7-1 168 3 1.75% 7-2 169 2 1.17% 1.0000 *, Fisher's exact test (-1 vs -2) Alignment files were compared to the reference genome (Hg19) using VarScan (PMID: 22728672) and any variant with at least 1 read in each direction was annotated using SnpEff (PMID: 22300766). To find variants that might contribute to growth after treatment, the list of variants was filtered to show only variants that were present at any frequency in both the "-1" and "-2" treatments for each sample. The seven variants discovered are shown on the table. Graphpad was used to perform a Fisher's Exact Test to determine whether the allele frequency in -1 was significantly different than the allele frequency in -2 based on the number of reference and alternate reads for each sample. Only variant, K318N, increased in frequency by a statistically significant amount: 7.88% to 27.91%. However, as this variant was only enriched in one of the four samples, it is unlikely to be a driving cause of recurrence and more likely to be selected by the driving force common to all four samples.