KEGG   PATHWAY: ko05202
Entry
ko05202                     Pathway                                
Name
Transcriptional misregulation in cancer
Description
In tumor cells, genes encoding transcription factors (TFs) are often amplified, deleted, rearranged via chromosomal translocation and inversion, or subjected to point mutations that result in a gain- or loss-of- function. In hematopoietic cancers and solid tumors, the translocations and inversions increase or deregulate transcription of the oncogene. Recurrent chromosome translocations generate novel fusion oncoproteins, which are common in myeloid cancers and soft-tissue sarcomas. The fusion proteins have aberrant transcriptional function compared to their wild-type counterparts. These fusion transcription factors alter expression of target genes, and thereby result in a variety of altered cellular properties that contribute to the tumourigenic process.
Class
Human Diseases; Cancer: overview
Pathway map
ko05202  Transcriptional misregulation in cancer
ko05202

Orthology
K00069  HPGD; 15-hydroxyprostaglandin dehydrogenase (NAD) [EC:1.1.1.141]
K00717  FUT8; glycoprotein 6-alpha-L-fucosyltransferase [EC:2.4.1.68]
K01327  ELANE; leukocyte elastase [EC:3.4.21.37]
K01343  PLAT; tissue plasminogen activator [EC:3.4.21.68]
K01348  PLAU; urokinase plasminogen activator [EC:3.4.21.73]
K01353  GZMB; granzyme B [EC:3.4.21.79]
K01394  MMP3; matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17]
K01403  MMP9; matrix metalloproteinase-9 (gelatinase B) [EC:3.4.24.35]
K01558  WNT16; wingless-type MMTV integration site family, member 16
K02159  BAX; apoptosis regulator BAX
K02162  BCL2A1; hematopoietic Bcl-2-related protein A1
K02211  CDK9; cyclin-dependent kinase 9 [EC:2.7.11.22 2.7.11.23]
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02583  NGFR, TNFRSF16, CD271; tumor necrosis factor receptor superfamily member 16
K02633  PER2; period circadian protein 2
K03160  TNFRSF5, CD40; tumor necrosis factor receptor superfamily member 5
K03172  TRAF1; TNF receptor-associated factor 1
K03176  NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K03211  ETV6_7, yan; ETS translocation variant 6/7
K03511  POLK; DNA polymerase kappa [EC:2.7.7.7]
K04359  PDGFA; platelet-derived growth factor subunit A
K04376  ELK4, SAP1; ETS domain-containing protein Elk-4
K04377  MYC; Myc proto-oncogene protein
K04387  IL1R2, CD121b; interleukin 1 receptor type II
K04388  TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]
K04391  CD14; monocyte differentiation antigen CD14
K04402  GADD45; growth arrest and DNA-damage-inducible protein
K04451  TP53, P53; tumor protein p53
K04452  DDIT3, GADD153; DNA damage-inducible transcript 3
K04453  MAX; Max protein
K04454  MEF2C; MADS-box transcription enhancer factor 2C
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04650  NCOR1, N-CoR; nuclear receptor co-repressor 1
K04676  SMAD1; mothers against decapentaplegic homolog 1
K04684  SP1; transcription factor Sp1
K04728  ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]
K04735  RELA; transcription factor p65
K04736  IL3; interleukin 3
K05069  IL2RB, CD122; interleukin 2 receptor beta
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05090  CSF1R, FMS, CD115; macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05092  FLT3, FLK2, CD135; fms-related tyrosine kinase 3 [EC:2.7.10.1]
K05096  FLT1, VEGFR1; FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05099  MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05199  GRIA3; glutamate receptor 3
K05230  DEFA; defensin, alpha
K05405  IL6; interleukin 6
K05413  CD86; CD86 antigen
K05427  CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor
K05459  IGF1; insulin-like growth factor 1
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K06056  PTCRA; pre T-cell antigen receptor alpha
K06067  HDAC1_2; histone deacetylase 1/2 [EC:3.5.1.98]
K06461  ITGAM, CD11b; integrin alpha M
K06498  FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I
K06532  PROM1, CD133; prominin 1
K06571  TSPAN7, TM4SF2, MXS1, CD231; tetraspanin-7
K06590  ITGB7; integrin beta 7
K06622  CDKN2C, P18, INK4C; cyclin-dependent kinase inhibitor 2C
K06624  CDKN1B, P27, KIP1; cyclin-dependent kinase inhibitor 1B
K06625  CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06627  CCNA; cyclin-A
K06643  MDM2; E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K06856  IGH; immunoglobulin heavy chain
K07201  FOXO1; forkhead box protein O1
K08024  HHEX, HEX, PRH; homeobox protein HEX
K08367  RUNX1, AML1; runt-related transcription factor 1
K08524  RXRA, NR2B1; retinoid X receptor alpha
K08525  RXRB, NR2B2; retinoid X receptor beta
K08526  RXRG, NR2B3; retinoid X receptor gamma
K08527  RARA, NR1B1; retinoic acid receptor alpha
K08530  NR1C3, PPARG; peroxisome proliferator-activated receptor gamma
K08559  NR4A3, NOR1; nuclear receptor subfamily 4 group A member 3
K08821  CDK14, PFTK1; cyclin-dependent kinase 14 [EC:2.7.11.22]
K08854  BMP2K, BIKE; BMP2 inducible kinase [EC:2.7.11.1]
K09035  CMAF, MAF; transcription factor Maf
K09053  ATF1; activating transcription factor 1
K09055  CEBPA; CCAAT/enhancer binding protein (C/EBP), alpha
K09063  TCF3, E2A; transcription factor E2-alpha
K09105  TFE3; transcription factor E3
K09109  NMYC, MYCN; N-myc proto-oncogene protein
K09186  MLL1; [histone H3]-lysine4 N-trimethyltransferase MLL1 [EC:2.1.1.354]
K09234  WT1; Wilms tumor protein 1
K09254  REL; c-Rel proto-oncogene protein
K09278  RUNX2, AML3; runt-related transcription factor 2
K09283  HMGA2; high mobility group AT-hook protein 2
K09293  PAX8; paired box protein 8
K09299  ZEB1; zinc finger homeobox protein 1
K09340  TLX1, HOX11; T-cell leukemia homeobox protein 1
K09355  PBX1; pre-B-cell leukemia transcription factor 1
K09381  PAX3_7; paired box protein 3/7
K09383  PAX5; paired box protein 5
K09431  ETV1; ets translocation variant 1
K09435  ERG; transcriptional regulator ERG
K09436  FLI1; friend leukemia integration 1 transcription factor
K09437  FEV; ETS oncogene family protein FEV
K09438  SPI1; transcription factor PU.1
K09455  MITF; microphthalmia-associated transcription factor
K09633  TMPRSS2; transmembrane protease serine 2 [EC:3.4.21.122]
K10030  IL8, CXCL8; interleukin 8
K10048  CEBPB; CCAAT/enhancer binding protein (C/EBP), beta
K10051  CEBPE; CCAAT/enhancer binding protein (C/EBP), epsilon
K10053  RUNX1T1, CBFA2T1; CBFA2/RNUX1 translocation partner 1
K10054  PML, TRIM19; E3 SUMO-protein ligase PML [EC:2.3.2.-]
K10055  ZBTB16, PLZF; zinc finger and BTB domain-containing protein 16
K10056  JUP, PG; junction plakoglobin
K10138  IGFBP3; insulin-like growth factor-binding protein 3
K10140  DDB2; DNA damage-binding protein 2
K10151  CCND2; G1/S-specific cyclin-D2
K10500  ZBTB17, MIZ1; zinc finger and BTB domain-containing protein 17
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K10789  MPO; myeloperoxidase [EC:1.11.2.2]
K11253  H3; histone H3
K11313  SUPT3H, SPT3; transcription initiation protein SPT3
K11424  WHSC1, MMSET, NSD2; [histone H3]-lysine36 N-dimethyltransferase NSD2 [EC:2.1.1.357]
K11427  DOT1L, DOT1; [histone H3]-lysine79 N-trimethyltransferase [EC:2.1.1.360]
K11447  UTX, KDM6A; lysine-specific demethylase 6A [EC:1.14.11.68]
K11449  JMJD1C; jumonji domain-containing protein 1C [EC:1.14.11.-]
K11459  PCGF4, BMI1; polycomb group RING finger protein 4
K11644  SIN3A; paired amphipathic helix protein Sin3a
K12823  DDX5, DBP2; ATP-dependent RNA helicase DDX5/DBP2 [EC:5.6.2.7]
K13098  TLS, FUS; RNA-binding protein FUS
K13105  PRCC; proline-rich protein PRCC
K13209  EWSR1; RNA-binding protein EWS
K14021  BAK, BAK1; Bcl-2 homologous antagonist/killer
K14242  NFKBIZ; NF-kappa-B inhibitor zeta
K14651  TAF15, NPL3; transcription initiation factor TFIID subunit 15
K14970  MEN1, MNN1; menin
K15184  AFF1; AF4/FMR2 family member 1
K15187  MLLT1_3, ENL, AF9; YEATS domain-containing protein 1/3
K15188  CCNT; cyclin T
K15379  SLC45A3; solute carrier family 45, member 3
K15589  ARNT2; aryl hydrocarbon receptor nuclear translocator 2
K15592  ETV4; ets translocation variant 4
K15593  ETV5; ets translocation variant 5
K15604  LYL1; protein lyl-1
K15605  KLF3; krueppel-like factor 3
K15607  TLX3, HOX11L2; T-cell leukemia homeobox protein 3
K15610  PBX3; pre-B-cell leukemia transcription factor 3
K15612  LMO2; rhombotin-2
K15613  MEIS1; homeobox protein Meis1
K15614  SIX1; homeobox protein SIX1
K15615  SIX4; homeobox protein SIX4
K15616  EYA1; eyes absent homolog 1 [EC:3.1.3.48]
K15617  LDB1; LIM domain-binding protein 1
K15618  BCL6; B-cell lymphoma 6 protein
K15619  SPINT1; Kunitz-type protease inhibitor 1
K15621  BAIAP3; BAI1-associated protein 3
K15622  MLF1; myeloid leukemia factor 1
K15623  SS18, SSXT, SYT, CREST; protein SSXT
K15624  SSX; protein SSX
K15626  NUPR1, COM1; nuclear protein 1
K15627  ASPSCR1, ASPL; tether containing UBX domain for GLUT4
K16060  BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K17443  HOXA10; homrobox protein Hox-A10
K17693  ID2; DNA-binding protein inhibitor ID2
K21946  DUSP6; dual specificity phosphatase 6 [EC:3.1.3.16 3.1.3.48]
K21950  HOXA9; homeobox protein Hox-A9
K21951  HOXA11; homeobox protein Hox-A11
K22046  BCL11B; B-cell lymphoma/leukemia 11B
Reference
PMID:11607818
  Authors
Alcalay M, Orleth A, Sebastiani C, Meani N, Chiaradonna F, Casciari C, Sciurpi MT, Gelmetti V, Riganelli D, Minucci S, Fagioli M, Pelicci PG
  Title
Common themes in the pathogenesis of acute myeloid leukemia.
  Journal
Oncogene 20:5680-94 (2001)
DOI:10.1038/sj.onc.1204642
Reference
PMID:12032780
  Authors
Scandura JM, Boccuni P, Cammenga J, Nimer SD
  Title
Transcription factor fusions in acute leukemia: variations on a theme.
  Journal
Oncogene 21:3422-44 (2002)
DOI:10.1038/sj.onc.1205315
Reference
PMID:12529654
  Authors
Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C
  Title
New mechanisms of AML1 gene alteration in hematological malignancies.
  Journal
Leukemia 17:9-16 (2003)
DOI:10.1038/sj.leu.2402766
Reference
PMID:10717473
  Authors
Lutterbach B, Hiebert SW
  Title
Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation.
  Journal
Gene 245:223-35 (2000)
DOI:10.1016/S0378-1119(00)00014-7
Reference
PMID:19075268
  Authors
Koschmieder S, Halmos B, Levantini E, Tenen DG
  Title
Dysregulation of the C/EBPalpha differentiation pathway in human cancer.
  Journal
J Clin Oncol 27:619-28 (2009)
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Reference
PMID:11340171
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Johansen LM, Iwama A, Lodie TA, Sasaki K, Felsher DW, Golub TR, Tenen DG
  Title
c-Myc is a critical target for c/EBPalpha in granulopoiesis.
  Journal
Mol Cell Biol 21:3789-806 (2001)
DOI:10.1128/MCB.21.11.3789-3806.2001
Reference
PMID:15985538
  Authors
Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann WK, Koeffler HP
  Title
Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia.
  Journal
Blood 106:2827-36 (2005)
DOI:10.1182/blood-2005-01-0358
Reference
PMID:12393465
  Authors
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  Title
The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia.
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Blood 101:270-7 (2003)
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Reference
PMID:12130514
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  Title
Heterozygous PU.1 mutations are associated with acute myeloid leukemia.
  Journal
Blood 100:998-1007 (2002)
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Reference
PMID:15160934
  Authors
Jing Y
  Title
The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia.
  Journal
Leuk Lymphoma 45:639-48 (2004)
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Reference
PMID:15024077
  Authors
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  Title
Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells.
  Journal
Mol Cell Biol 24:2890-904 (2004)
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Reference
PMID:19855079
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  Title
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  Journal
Blood 114:5499-511 (2009)
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Reference
PMID:10500199
  Authors
McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR, Murre C
  Title
Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia.
  Journal
Proc Natl Acad Sci U S A 96:11464-9 (1999)
DOI:10.1073/pnas.96.20.11464
Reference
PMID:15156184
  Authors
Zelent A, Greaves M, Enver T
  Title
Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia.
  Journal
Oncogene 23:4275-83 (2004)
DOI:10.1038/sj.onc.1207672
Reference
PMID:14630078
  Authors
Sawinska M, Ladon D
  Title
Mechanism, detection and clinical significance of the reciprocal translocation t(12;21)(p12;q22) in the children suffering from acute lymphoblastic leukaemia.
  Journal
Leuk Res 28:35-42 (2004)
DOI:10.1016/S0145-2126(03)00160-7
Reference
PMID:19141473
  Authors
Guenther MG, Lawton LN, Rozovskaia T, Frampton GM, Levine SS, Volkert TL, Croce CM, Nakamura T, Canaani E, Young RA
  Title
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.
  Journal
Genes Dev 22:3403-8 (2008)
DOI:10.1101/gad.1741408
Reference
PMID:16169901
  Authors
Xia ZB, Popovic R, Chen J, Theisler C, Stuart T, Santillan DA, Erfurth F, Diaz MO, Zeleznik-Le NJ
  Title
The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression.
  Journal
Proc Natl Acad Sci U S A 102:14028-33 (2005)
DOI:10.1073/pnas.0506464102
Reference
PMID:21518926
  Authors
Wang QF, Wu G, Mi S, He F, Wu J, Dong J, Luo RT, Mattison R, Kaberlein JJ, Prabhakar S, Ji H, Thirman MJ
  Title
MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome.
  Journal
Blood 117:6895-905 (2011)
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Reference
PMID:14701735
  Authors
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  Title
Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization.
  Journal
Mol Cell Biol 24:617-28 (2004)
DOI:10.1128/MCB.24.2.617-628.2004
Reference
PMID:19133982
  Authors
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  Title
Role of TLX1 in T-cell acute lymphoblastic leukaemia pathogenesis.
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Br J Haematol 145:140-3 (2009)
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Reference
PMID:12511414
  Authors
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Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma.
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Blood 101:3681-6 (2003)
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Reference
PMID:11313274
  Authors
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Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells.
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Blood 97:2798-807 (2001)
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Reference
PMID:12670461
  Authors
Zuzel M, Cawley JC.
  Title
The biology of hairy cells.
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Best Pract Res Clin Haematol 16:1-13 (2003)
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Reference
PMID:14998494
  Authors
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  Title
Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.
  Journal
Cancer Cell 5:191-9 (2004)
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Reference
PMID:20974671
  Authors
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  Title
The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells.
  Journal
Blood 117:211-20 (2011)
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Reference
PMID:19059936
  Authors
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  Title
MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells.
  Journal
Haematologica 94:78-86 (2009)
DOI:10.3324/haematol.13426
Reference
PMID:10350329
  Authors
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  Title
Chromosomal rearrangement of the PAX-5 locus in lymphoplasmacytic lymphoma with t(9;14)(p13;q32).
  Journal
Leuk Lymphoma 34:25-33 (1999)
DOI:10.3109/10428199909083377
Reference
PMID:10784387
  Authors
Ohno H, Ueda C, Akasaka T
  Title
The t(9;14)(p13;q32) translocation in B-cell non-Hodgkin's lymphoma.
  Journal
Leuk Lymphoma 36:435-45 (2000)
DOI:10.3109/10428190009148390
Reference
PMID:19233641
  Authors
Prensner JR, Chinnaiyan AM
  Title
Oncogenic gene fusions in epithelial carcinomas.
  Journal
Curr Opin Genet Dev 19:82-91 (2009)
DOI:10.1016/j.gde.2008.11.008
Reference
PMID:19406209
  Authors
Brenner JC, Chinnaiyan AM
  Title
Translocations in epithelial cancers.
  Journal
Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005
Reference
PMID:16946003
  Authors
Reddi HV, McIver B, Grebe SK, Eberhardt NL
  Title
The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis.
  Journal
Endocrinology 148:932-5 (2007)
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Reference
PMID:19422821
  Authors
Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG
  Title
The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay.
  Journal
Exp Cell Res 315:2399-409 (2009)
DOI:10.1016/j.yexcr.2009.04.022
Reference
PMID:18563191
  Authors
Kumar-Sinha C, Tomlins SA, Chinnaiyan AM
  Title
Recurrent gene fusions in prostate cancer.
  Journal
Nat Rev Cancer 8:497-511 (2008)
DOI:10.1038/nrc2402
Reference
PMID:20478527
  Authors
Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM
  Title
An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
  Journal
Cancer Cell 17:443-54 (2010)
DOI:10.1016/j.ccr.2010.03.018
Reference
PMID:21747944
  Authors
Leshem O, Madar S, Kogan-Sakin I, Kamer I, Goldstein I, Brosh R, Cohen Y, Jacob-Hirsch J, Ehrlich M, Ben-Sasson S, Goldfinger N, Loewenthal R, Gazit E, Rotter V, Berger R
  Title
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
  Journal
PLoS One 6:e21650 (2011)
DOI:10.1371/journal.pone.0021650
Reference
PMID:17505060
  Authors
Cai C, Hsieh CL, Omwancha J, Zheng Z, Chen SY, Baert JL, Shemshedini L
  Title
ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion.
  Journal
Mol Endocrinol 21:1835-46 (2007)
DOI:10.1210/me.2006-0480
Reference
PMID:18172298
  Authors
Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
  Title
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
  Journal
Cancer Res 68:73-80 (2008)
DOI:10.1158/0008-5472.CAN-07-5352
Reference
PMID:21849159
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Related
pathway
ko04115  p53 signaling pathway
ko05211  Renal cell carcinoma
ko05215  Prostate cancer
ko05216  Thyroid cancer
ko05221  Acute myeloid leukemia

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