Supplementary Table 2b. List of spliced oncogenes and tumor suppressors identified in AML patients compared to normal donors
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1 1 Supplementary Table 2b. List of spliced oncogenes and tumor suppressors identified in AML patients compared to normal donors Gene Symbol Gene Name / Tumor Suppressors AKT1 v-akt murine thymoma viral oncogene homolog 1 v-raf v-raf murine sarcoma 3611 viral oncogene homolog BCL2 B-cell CLL/lymphoma 2 BCR breakpoint cluster region BRAF v-raf murine sarcoma viral oncogene homolog B1 BRCA1 breast cancer 1, early onset CASP8 caspase 8, apoptosis-related cysteine peptidase CBLB Cas-Br-M (murine) ecotropic retroviral transforming sequence b CCND2 cyclin D2 CDC42 cell division cycle 42 (GTP binding protein, 25kDa) CENTG1 centaurin, gamma 1 CSF1R colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog DAPK1 death-associated protein kinase 1 ETS1 v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) FGFR1 fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome) FOS v-fos FBJ murine osteosarcoma viral oncogene homolog HEXB hexosaminidase B (beta polypeptide) HIF1A hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 IL8 interleukin 8 ITGB1 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) JUN jun oncogene JUP junction plakoglobin KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog MAP2K3 mitogen-activated protein kinase kinase 3 MCM3 minichromosome maintenance complex component 3 NCOA4 nuclear receptor coactivator 4 PAK1 p21/cdc42/rac1-activated kinase 1 (STE20 homolog, yeast) PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific) PML promyelocytic leukemia PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)
2 2 RAB31 RAB31, member RAS oncogene family RAB5B RAB5B, member RAS oncogene family RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1 SNRPE small nuclear ribonucleoprotein polypeptide E SOS1 son of sevenless homolog 1 (Drosophila) THOC4 THO complex 4 TPR translocated promoter region (to activated MET oncogene) VAV1 vav 1 oncogene VAV3 vav 3 oncogene CXCR4 chemokine (C-X-C motif) receptor 4 NFKB1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide PRKAR1A protein kinase, camp-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) PTGS2 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) RB1 retinoblastoma 1 (including osteosarcoma) RELA v-rel reticuloendotheliosis viral oncogene homolog A RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1) STAT3 signal transducer and activator of transcription 3 UBE3A ubiquitin protein ligase E3A TP53 tumor protein p53 (Li-Fraumeni syndrome) Tumor Suppressor ARRB2 arrestin, beta 2 Tumor Suppressors ATM ataxia telangiectasia mutated (includes complementation groups A, C and D) Tumor Suppressors 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
3 3 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 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) Tumor Suppressors NR4A1 nuclear receptor subfamily 4, group A, member 1 Tumor Suppressors PECAM1 platelet/endothelial cell adhesion molecule (CD31 antigen) Tumor Suppressors PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform Tumor Suppressors 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 spleen 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 YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide Tumor Suppressors 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 genes that are listed in this table. Splice variants of these genes were recurrently detected in AML patients as compared to normal donors.
4 4 Supplementary Table 2c. List of genes spliced in both DFCI and UHN cohorts and absent in normal donors Differentially spliced gene symbol DFCI cohort (# of patients) UHN cohort (# of patients) RPS TRBV TNFSF12-TNFSF GOLGA CTNND PVRL HLA-C CHD HSPG UPK3B FLJ IGLV USP EEF1A C13ORF RPA NAIP 9 29 IGKC MAP3K MARVELD FLJ LTF HLA-DRB PDE4B MPL ARHGAP WDR MARK PRG PRKDC MLL TIMELESS TSC22D DDX MED12L RTN PRDM DOCK PDE4D DNTT AFF SEC31A KIAA
5 5 UBAP SNORD EDD JMJD MSX2P MLL TBL1X 9 22 PDE4DIP SRGN CAST CREBL ERC BAZ1B CBLB PTPN ATM 9 21 ITGA PKD RUNX FABP SLC44A SRRM BAT2D SF CFD APP MPO ARHGEF EPB STXBP LTBP BAZ1A PLXND SLC7A5P HDAC7A HDAC ZDHHC ANK HD HLA-DQA RBM ZUBR SPTA BMS TNS GOLGA8A LYST 10 18
6 6 C1ORF PTPRC HERC WHSC RARS HIPK IGLL ATRN ARHGAP HERC ZNF ZMYM BIRC VCAN NOTCH PDCD MACF KIAA DCTN ITGAX POLR2A MED ANAPC CA DPYSL PCAF GOLGA8B FOSB 9 16 MYCBP DOCK PTPRA TXNDC BPTF EIF4G MLL SORL SMARCA GTF2I NIPBL TTLL VCL FAM38A JARID1B CDK5RAP PTPRS HIST1H2AG DDEF
7 7 HIST1H3D LY DUT AGTPBP RNF FLT SFXN RERE 9 14 CD UBE2L SRBD ATXN LARS WNK DOCK PROM LEPROT JUP TOP2A FNDC3B PRAM TBCD MKI RABGAP1L SPTAN MAN1A MEF2C 9 13 WDR CD IDS 8 13 LGMN SYNE HIST1H2AC PHKB UBAC C2ORF FMNL NIN CHD FGR BNIP3L GUCY1A LILRB NCOR CHD COG EMR
8 8 ATP2C TRAK OAS GTF3C MDN CDC ILF NCAPD FCN UBE3C FNIP UBAP2L VAV SMARCA SLC7A5P APBB1IP EIF3S CLTC MEIS ME SIN3A EIF4G MCTP SIDT F11R GSTM SLC2A DDX WWP PPRC CPNE HLA-B 15 9 HIST1H1C 12 9 PRDX ASH1L 11 9 ZC3HAV ATE1 9 9 ZMYND MALAT UQCRC FANCI 12 8 HBA ATP2B OGT 10 8 ANXA BRPF ST7 9 8
9 9 DMXL1 9 8 CLASP1 9 8 MLL4 9 8 GIT2 9 8 PXDNL 18 7 TGFBI 16 7 CD TTC SMC1A 10 7 DNAJB CHST2 9 7 SNORA ACTN EHMT WDR40A 10 6 PDHA1 9 6 SETD3 9 6 SEL1L 9 6 HSPA1A 12 5 BCL FHL MBOAT SEPT CTSG 12 4 OGDH 9 4 SAMHD1 9 4 CDC42BPA 9 4 PCNT 11 3 SLC2A PRKACB 10 2 MLL3 9 2 RAB8B 16 1 FTH BPGM 10 1 NUP98 21 FLJ COL24A1 19 NCAPH 18 DDX3Y 17 CUL1 15 SFRS1 15 PFAS 15 ZBTB44 15 FAM120A 13 SAFB2 13 ABHD2 13 DOCK1 13
10 10 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 C14ORF ADRBK1 10 ZRANB1 10 SUPV3L1 10 CCDC7 10 USP33 10 EEF1A1 9 PHIP 9 MAN2A1 9 RICTOR 9 KLHL24 9 PLSCR1 9
11 11 DIRC2 9 NUP50 9 C21ORF59 9 SP100 9 CXCR4 9 KPNA2 9 MGC BIRC5 9 SUPT4H1 9 NFAT5 9 MT2A 9 SMG1 9 ZFAND6 9 KIAA 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.
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