Adamia et al. 1 Aberrant Splicing in AML

Supplementary Table 2b. List of spliced oncogenes and tumor suppressors identified in AML patients compared to normal donors

Oncogenes/ Symbol Gene Name Tumor Suppressors AKT1 v-akt murine thymoma viral oncogene homolog 1 Oncogenes v-RAF v-raf murine sarcoma 3611 viral oncogene homolog Oncogenes BCL2 B-cell CLL/ 2 Oncogenes BCR breakpoint cluster region Oncogenes BRAF v-raf murine sarcoma viral oncogene homolog B1 Oncogenes BRCA1 breast cancer 1, early onset Oncogenes CASP8 caspase 8, apoptosis-related cysteine peptidase Oncogenes CBLB Cas-Br-M (murine) ecotropic retroviral transforming sequence b Oncogenes CCND2 cyclin D2 Oncogenes CDC42 cell division cycle 42 (GTP binding , 25kDa) Oncogenes CENTG1 centaurin, gamma 1 Oncogenes colony stimulating factor 1 , formerly McDonough feline CSF1R Oncogenes sarcoma viral (v-fms) oncogene homolog DAPK1 death-associated 1 Oncogenes ETS1 v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) Oncogenes fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, FGFR1 Oncogenes Pfeiffer syndrome) FOS v-fos FBJ murine osteosarcoma viral oncogene homolog Oncogenes HEXB hexosaminidase B (beta polypeptide) Oncogenes hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix HIF1A Oncogenes factor) HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 Oncogenes IL8 Oncogenes integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen ITGB1 Oncogenes CD29 includes MDF2, MSK12) JUN jun oncogene Oncogenes JUP junction plakoglobin Oncogenes KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Oncogenes LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog Oncogenes MAP2K3 mitogen-activated protein kinase kinase 3 Oncogenes MCM3 minichromosome maintenance complex component 3 Oncogenes NCOA4 4 Oncogenes PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast) Oncogenes PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide Oncogenes PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific) Oncogenes PML promyelocytic leukemia Oncogenes protein tyrosine phosphatase, non-receptor type 11 (Noonan PTPN11 Oncogenes syndrome 1) Adamia et al. 2 Aberrant Splicing in AML

RAB31 RAB31, member RAS oncogene family Oncogenes RAB5B RAB5B, member RAS oncogene family Oncogenes RAPGEF1 Rap guanine exchange factor (GEF) 1 Oncogenes SNRPE small nuclear ribonucleoprotein polypeptide E Oncogenes SOS1 homolog 1 (Drosophila) Oncogenes THOC4 THO complex 4 Oncogenes TPR translocated region (to activated MET oncogene) Oncogenes VAV1 vav 1 oncogene Oncogenes VAV3 vav 3 oncogene Oncogenes CXCR4 (C-X-C motif) receptor 4 Oncogenes nuclear factor of kappa light polypeptide gene enhancer in B-cells NFKB1 Oncogenes 1 (p105) PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide Oncogenes protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue PRKAR1A Oncogenes specific extinguisher 1) prostaglandin-endoperoxide synthase 2 (prostaglandin G/H PTGS2 Oncogenes synthase and cyclooxygenase) RB1 retinoblastoma 1 (including osteosarcoma) Oncogenes RELA v- reticuloendotheliosis viral oncogene homolog A Oncogenes RUNX1 runt-related 1 (acute myeloid leukemia 1) Oncogenes STAT3 signal transducer and activator of transcription 3 Oncogenes UBE3A ubiquitin protein ligase E3A Oncogenes TP53 tumor protein (Li-Fraumeni syndrome) Tumor Suppressor ARRB2 arrestin, beta 2 Tumor Suppressors ataxia telangiectasia mutated (includes complementation groups ATM Tumor Suppressors A, C and D) BIRC5 baculoviral IAP repeat-containing 5 (survivin) Tumor Suppressors CD4 CD4 molecule Tumor Suppressors CD59 CD59 molecule, complement regulatory protein Tumor Suppressors CD81 CD81 molecule Tumor Suppressors CDC14A CDC14 cell division cycle 14 homolog A (S. cerevisiae) Tumor Suppressors CFLAR CASP8 and FADD-like apoptosis regulator Tumor Suppressors CREB1 cAMP responsive element binding protein 1 Tumor Suppressors CREBBP CREB binding protein (Rubinstein-Taybi syndrome) Tumor Suppressors CUL1 cullin 1 Tumor Suppressors DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae) Tumor Suppressors DUSP6 dual specificity phosphatase 6 Tumor Suppressors ENO1 enolase 1, (alpha) Tumor Suppressors FLNA filamin A, alpha (actin binding protein 280) Tumor Suppressors FLT3 fms-related tyrosine kinase 3 Tumor Suppressors FRAP1 FK506 binding protein 12-rapamycin associated protein 1 Tumor Suppressors GSTP1 glutathione S-transferase pi Tumor Suppressors Adamia et al. 3 Aberrant Splicing in AML

HDAC2 histone deacetylase 2 Tumor Suppressors IGF1R insulin-like growth factor 1 receptor Tumor Suppressors INPP4B inositol polyphosphate-4-phosphatase, type II, 105kDa Tumor Suppressors ITGA5 integrin, alpha 5 (fibronectin receptor, alpha polypeptide) Tumor Suppressors ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) Tumor Suppressors JAK2 Janus kinase 2 (a protein tyrosine kinase) Tumor Suppressors MAP3K4 mitogen-activated protein kinase kinase kinase 4 Tumor Suppressors MAPK14 mitogen-activated protein kinase 14 Tumor Suppressors MAPK8 mitogen-activated protein kinase 8 Tumor Suppressors MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) Tumor Suppressors (neurofibromatosis, von Recklinghausen disease, NF1 Tumor Suppressors Watson disease) NR4A1 nuclear receptor subfamily 4, group A, member 1 Tumor Suppressors PECAM1 platelet/endothelial cell adhesion molecule (CD31 antigen) Tumor Suppressors protein phosphatase 1A (formerly 2C), magnesium-dependent, PPM1A Tumor Suppressors alpha isoform PRDM4 PR domain containing 4 Tumor Suppressors PRKCD protein kinase C, delta Tumor Suppressors PTPRJ protein tyrosine phosphatase, receptor type, J Tumor Suppressors RBL1 retinoblastoma-like 1 (p107) Tumor Suppressors SMAD2 SMAD family member 2 Tumor Suppressors SMAD3 SMAD family member 3 Tumor Suppressors SMAD4 SMAD family member 4 Tumor Suppressors STAT5A signal transducer and activator of transcription 5A Tumor Suppressors STK3 serine/threonine kinase 3 (STE20 homolog, yeast) Tumor Suppressors STK4 serine/threonine kinase 4 Tumor Suppressors SYK tyrosine kinase Tumor Suppressors TRAF6 TNF receptor-associated factor 6 Tumor Suppressors TUSC4 tumor suppressor candidate 4 Tumor Suppressors UBE4B ubiquitination factor E4B (UFD2 homolog, yeast) Tumor Suppressors WASL Wiskott-Aldrich syndrome-like Tumor Suppressors tyrosine 3-monooxygenase/tryptophan 5-monooxygenase YWHAE Tumor Suppressors activation protein, epsilon polypeptide ZYX zyxin Tumor Suppressors

Annotation analyses of the differentially spliced transcripts detected in both DFCI and UHN cohorts identified novel splice variants of 52 oncogenes and 50 tumor suppressor that are listed in this table. Splice variants of these genes were recurrently detected in AML patients as compared to normal donors. Adamia et al. 4 Aberrant Splicing in AML

Supplementary Table 2c. List of genes spliced in both DFCI and UHN cohorts and absent in normal donors

Differentially spliced gene DFCI cohort UHN cohort symbol (# of patients) (# of patients) RPS8 29 34 TRBV3-1 24 33 TNFSF12-TNFSF13 13 33 GOLGA2 12 32 CTNND1 17 31 PVRL1 11 31 HLA-C 25 30 CHD3 16 30 HSPG2 16 30 UPK3B 14 30 FLJ12529 10 30 IGLV3-25 22 29 USP11 19 29 EEF1A1 18 29 C13ORF23 15 29 RPA1 11 29 NAIP 9 29 IGKC 15 28 MAP3K4 13 28 MARVELD1 12 28 FLJ10292 9 28 LTF 23 27 HLA-DRB5 19 27 PDE4B 17 27 MPL 14 27 ARHGAP4 10 27 WDR70 10 27 MARK2 10 27 PRG2 22 26 PRKDC 19 26 MLL3 11 26 TIMELESS 17 25 TSC22D1 15 25 DDX11 14 25 MED12L 13 25 RTN4 19 24 PRDM2 11 24 DOCK2 9 24 PDE4D 25 23 DNTT 22 23 AFF2 18 23 SEC31A 18 23 KIAA0182 16 23 Adamia et al. 5 Aberrant Splicing in AML

UBAP2 12 23 SNORD41 9 23 EDD1 14 22 JMJD6 14 22 MSX2P 14 22 MLL2 11 22 TBL1X 9 22 PDE4DIP 22 21 SRGN 18 21 CAST 16 21 CREBL1 11 21 ERC1 11 21 BAZ1B 10 21 CBLB 10 21 PTPN23 9 21 ATM 9 21 ITGA4 18 20 PKD1 17 20 RUNX1 16 20 FABP5 14 20 SLC44A1 12 20 SRRM2 12 20 BAT2D1 12 20 SF1 9 20 CFD 18 19 APP 16 19 MPO 15 19 ARHGEF12 15 19 EPB42 14 19 STXBP5 13 19 LTBP1 13 19 BAZ1A 11 19 PLXND1 10 19 SLC7A5P1 10 19 HDAC7A 10 19 HDAC5 9 19 ZDHHC17 9 19 ANK1 19 18 HD 17 18 HLA-DQA1 16 18 RBM12 15 18 ZUBR1 15 18 SPTA1 13 18 BMS1 12 18 TNS1 10 18 GOLGA8A 10 18 LYST 10 18 Adamia et al. 6 Aberrant Splicing in AML

C1ORF164 23 17 PTPRC 18 17 HERC2 15 17 WHSC1 14 17 RARS 13 17 HIPK3 13 17 IGLL1 12 17 ATRN 12 17 ARHGAP12 11 17 HERC4 10 17 ZNF217 9 17 ZMYM6 22 16 BIRC6 20 16 VCAN 17 16 NOTCH2 16 16 PDCD11 15 16 MACF1 15 16 KIAA1797 13 16 DCTN1 13 16 ITGAX 13 16 POLR2A 12 16 MED12 11 16 ANAPC1 11 16 CA1 10 16 DPYSL2 10 16 PCAF 10 16 GOLGA8B 10 16 FOSB 9 16 MYCBP2 9 16 DOCK8 18 15 PTPRA 17 15 TXNDC5 14 15 BPTF 13 15 EIF4G3 13 15 MLL5 12 15 SORL1 12 15 SMARCA2 11 15 GTF2I 11 15 NIPBL 11 15 TTLL12 11 15 VCL 11 15 FAM38A 10 15 JARID1B 10 15 CDK5RAP3 9 15 PTPRS 18 14 HIST1H2AG 16 14 DDEF1 15 14 Adamia et al. 7 Aberrant Splicing in AML

HIST1H3D 13 14 LY75 12 14 DUT 12 14 AGTPBP1 11 14 RNF123 10 14 FLT3 10 14 SFXN4 10 14 RERE 9 14 CD36 15 13 UBE2L3 15 13 SRBD1 15 13 ATXN2 15 13 LARS 14 13 WNK1 14 13 DOCK11 13 13 PROM1 13 13 LEPROT 13 13 JUP 12 13 TOP2A 12 13 FNDC3B 11 13 PRAM1 11 13 TBCD 10 13 MKI67 10 13 RABGAP1L 10 13 SPTAN1 9 13 MAN1A1 9 13 MEF2C 9 13 WDR68 9 13 CD59 9 13 IDS 8 13 LGMN 18 12 SYNE1 15 12 HIST1H2AC 15 12 PHKB 15 12 UBAC2 15 12 C2ORF28 14 12 FMNL1 14 12 NIN 13 12 CHD2 12 12 FGR 12 12 BNIP3L 11 12 GUCY1A3 11 12 LILRB2 11 12 NCOR1 11 12 CHD9 11 12 COG5 10 12 EMR2 10 12 Adamia et al. 8 Aberrant Splicing in AML

ATP2C1 9 12 TRAK2 9 12 OAS3 9 12 GTF3C2 16 11 MDN1 13 11 CDC37 13 11 ILF3 12 11 NCAPD2 12 11 FCN1 11 11 UBE3C 11 11 FNIP1 11 11 UBAP2L 11 11 VAV1 10 11 SMARCA5 9 11 SLC7A5P1 21 10 APBB1IP 21 10 EIF3S4 14 10 CLTC 14 10 MEIS1 13 10 ME2 12 10 SIN3A 12 10 EIF4G1 11 10 MCTP2 11 10 SIDT2 11 10 F11R 11 10 GSTM1 11 10 SLC2A5 11 10 DDX17 10 10 WWP2 10 10 PPRC1 9 10 CPNE3 16 9 HLA-B 15 9 HIST1H1C 12 9 PRDX2 12 9 ASH1L 11 9 ZC3HAV1 10 9 ATE1 9 9 ZMYND8 15 8 MALAT1 14 8 UQCRC1 13 8 FANCI 12 8 HBA2 11 8 ATP2B1 11 8 OGT 10 8 ANXA5 10 8 BRPF1 10 8 ST7 9 8 Adamia et al. 9 Aberrant Splicing in AML

DMXL1 9 8 CLASP1 9 8 MLL4 9 8 GIT2 9 8 PXDNL 18 7 TGFBI 16 7 CD96 14 7 TTC17 12 7 SMC1A 10 7 DNAJB6 10 7 CHST2 9 7 SNORA18 17 6 ACTN4 13 6 EHMT1 10 6 WDR40A 10 6 PDHA1 9 6 SETD3 9 6 SEL1L 9 6 HSPA1A 12 5 BCL2 12 5 FHL1 10 5 MBOAT2 10 5 SEPT---9 9 5 CTSG 12 4 OGDH 9 4 SAMHD1 9 4 CDC42BPA 9 4 PCNT 11 3 SLC2A3 21 2 PRKACB 10 2 MLL3 9 2 RAB8B 16 1 FTH1 11 1 BPGM 10 1 NUP98 21 FLJ10120 19 COL24A1 19 NCAPH 18 DDX3Y 17 CUL1 15 SFRS1 15 PFAS 15 ZBTB44 15 FAM120A 13 SAFB2 13 ABHD2 13 DOCK1 13 Adamia et al. 10 Aberrant Splicing in AML

RBMX 13 BCL11A 12 PML 12 PPM1A 12 PNN 12 HNRPH3 12 TSC1 11 POMT1 11 TGFBR1 11 ANKRD17 11 SMC4 11 L3MBTL2 11 HM13 11 PPP3R1 11 RIOK3 11 FANCA 11 ARHGAP5 11 ZDHHC20 11 NLRP3 11 IARS 10 JMJD2C 10 SMURF1 10 TBRG4 10 EEF1A1 10 ARID1B 10 HERC5 10 DOPEY2 10 C20ORF19 10 SP3 10 PSD4 10 AFF3 10 SOS1 10 DOT1L 10 CTDP1 10 RALBP1 10 C14ORF159 10 ADRBK1 10 ZRANB1 10 SUPV3L1 10 CCDC7 10 USP33 10 EEF1A1 9 PHIP 9 MAN2A1 9 RICTOR 9 KLHL24 9 PLSCR1 9 Adamia et al. 11 Aberrant Splicing in AML

DIRC2 9 NUP50 9 C21ORF59 9 SP100 9 CXCR4 9 KPNA2 9 MGC15523 9 BIRC5 9 SUPT4H1 9 NFAT5 9 MT2A 9 SMG1 9 ZFAND6 9 KIAA0831 9 CUL4A 9 EP400 9 PPHLN1 9 SNX15 9 PDCD4 9 ZDHHC16 9 SPOCK2 9 EIF2C3 9 FUSIP1 9 UTY 8 WWC3 8

This Table is summary of the analysis obtained by evaluating the extent of similarities between the

DFCI and UHN patient cohorts with respect to splicing event frequency. We found that 75% of the transcripts that were recurrently spliced in 30% or more of DFCI patient cohort were also recurrently spliced in the UHN patient cohort.