STANDARD_NAME SHEPARD_CRASH_AND_BURN_MUTANT_UP SYSTEMATIC_NAME M10828 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SHEPARD_CRASH_AND_BURN_MUTANT_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Human orthologs of genes up-regulated in the crb ('crash and burn') zebrafish mutant that represents a loss-of-function mutation in BMYB [GeneID=4605]. DESCRIPTION_FULL A major goal of cancer research has been to identify genes that contribute to cancer formation. The similar pathology between zebrafish and human tumors, as well as the past success of large-scale genetic screens in uncovering human disease genes, makes zebrafish an ideal system in which to find such new genes. Here, we show that a zebrafish forward genetic screen uncovered multiple cell proliferation mutants including one mutant, crash&burn (crb), that represents a loss-of-function mutation in bmyb, a transcriptional regulator and member of a putative proto-oncogene family. crb mutant embryos have defects in mitotic progression and spindle formation, and exhibit genome instability. Regulation of cyclin B levels by bmyb appears to be the mechanism of mitotic accumulation in crb. Carcinogenesis studies reveal increased cancer susceptibility in adult crb heterozygotes. Gene-expression signatures associated with loss of bmyb in zebrafish are also correlated with conserved signatures in human tumor samples, and down-regulation of the B-myb signature genes is associated with retention of p53 function. Our findings show that zebrafish screens can uncover cancer pathways, and demonstrate that loss of function of bmyb is associated with cancer. PMID 16150706 GEOID AUTHORS Shepard JL,Amatruda JF,Stern HM,Subramanian A,Finkelstein D,Ziai J,Finley KR,Pfaff KL,Hersey C,Zhou Y,Barut B,Freedman M,Lee C,Spitsbergen J,Neuberg D,Weber G,Golub TR,Glickman JN,Kutok JL,Aster JC,Zon LI CONTRIBUTOR Jennifer Shepard CONTRIBUTOR_ORG Broad Institute EXACT_SOURCE unknown FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABCF2,ADAM10,ADPRTL3,AK3L1,AKR7A2,ANGPTL3,ANKRD22,AP1M2,AP3M1,ARHCL1,ARMET,ATF3,ATPIF1,B3GNT1,BAX,BMP2,BOP1,BRF1,BTG2,BXDC1,C10orf119,C14orf21,C14orf58,C15orf12,C16orf7,C20orf142,C20orf155,C21orf33,C2GNT3,C6,C6orf11,C8orf4,CASP8,CCNG1,CCNG2,CDT6,CDX4,CEBPB,CGI-147,CGI-37,CGI-51,CIC,CIRH1A,CLDN4,CORT,CTH,CYP24A1,CYP26A1,CYP27B1,CYP51A1,CYR61,DDX49,DDX51,DKFZp434F,DKFZp564C,DKFZp566E144,DNAJA3,Dr.3096,DRG2,DSCR1,DT1P1A10,DUSP4,DUSP5,EGFL3,EGR1,EIF4E,ELOVL1,ERBP,ETF1,FBL,FLJ10292,FLJ10458,FLJ10460,FLJ10534,FLJ10842,FLJ11126,FLJ11184,FLJ11273,FLJ20244,FLJ20303,FLJ20718,FN1,FOS,FOXO3A,FST,FTSJ1,FTSJ3,GADD45B,GPD1,HARSL,HES1,HIG1,HIST1H3B,HOM-TES-103,HSPA1L,HSPA4,HSPA9B,HSPCA,IBRDC2,ID2,IGF2,IGFBP1,IMP4,IMPDH1,ING5,ITGB1BP3,ITGB4BP,JDP2,JUN,JUNB,KIAA0146,KIAA1587,KLF2,KRT17,LOC114971,LOC131076,LOC255374,LOC388962,LOC400916,LOC57149,LOC83693,LOC90139,MARS,MDM2,MGC3162,MIDN,MKNK2,MMP2,MMP9,MRPL12,MRPL22,MRPL52,MRPS18A,MRPS18B,MRPS26,MS4A4A,MYBBP1A,MYOG,NOC4,NOG,NOL6,NOL7,NOL8,NOLA1,NS,ODC1,P8,PAF53,PDLIM3,PES1,PFKFB3,PHLDA2,PIM1,PINX1,PLK3,POP4,PPAN,PPP1R14A,PRSS25,PTD004,PTGES2,PTGS2,PTP4A3,PWP1,QARS,RASL11B,RBP4,REA,RERG,RGC32,RNASET2,RNU3IP2,RPL10L,RPS27L,RRS1,SAS10,SAT,SEC23B,SERPINH1,SGK,SHMT1,SIX2,SLC12A3,SLC12A7,SLC16A6,SLC3A2,SNAI1,SRPRB,SSR1,STARD10,TAF9,TIEG2,TOB1,TOMM20,TP53,TP53INP1,TPRT,TSFM,TUBA8,TXNIP,VRK2,WBSCR22,WDR12,WDR8,ZNF259,ZNF330,ZNF593,ZPR9 GENE_SYMBOLS ABCF2,ADAM10,PARP3,AK4,AKR7A2,ANGPTL3,ANKRD22,AP1M2,AP3M1,PPM1H,MANF,ATF3,ATP5IF1,B3GNT2,BAX,BMP2,BOP1,BRF1,BTG2,RPF2,MCMBP,NOP9,FLVCR2,IMP3,VPS9D1,FITM2,CRLS1,GATD3,GCNT4,C6,WDR46,TCIM,CASP8,CCNG1,CCNG2,ANGPTL7,CDX4,CEBPB,PTRH2,NIP7,SAMM50,CIC,UTP4,CLDN4,CORT,CTH,CYP24A1,CYP26A1,CYP27B1,CYP51A1,CCN1,DDX49,DDX51,,,REXO2,DNAJA3,DRG2,RCAN1,TSR2,DUSP4,DUSP5,,MEGF6,EGR1,EIF4E,ELOVL1,DNTTIP2,ETF1,FBL,MAGOHB,NLE1,HAUS2,TSR1,AGK,DDX19A,TMA16,TMEM106B,TRMT1,NSUN2,HEATR3,FN1,FOS,FOXO3,FST,FTSJ1,FTSJ3,GADD45B,GPD1,HARS2,HES1,HIGD1A,H3C2,IFFO1,HSPA1L,HSPA4,HSPA9,HSP90AA1,RNF144B,ID2,IGF2,IGFBP1,IMP4,IMPDH1,ING5,NMRK2,EIF6,JDP2,JUN,JUNB,SPIDR,MAGEE1,KLF2,KRT17,PTPMT1,MIX23,MBLAC1,BOLA3,CHCHD10,LYRM1,HSDL1,TSPAN18,MARS1,MDM2,NOC4L,MIDN,MKNK2,MMP2,MMP9,MRPL12,MRPL22,MRPL52,MRPS18A,MRPS18B,MRPS26,MS4A4A,MYBBP1A,MYOG,EMC8,NOG,NOL6,NOL7,NOL8,GAR1,SPINK5,ODC1,S100A8,POLR1E,PDLIM3,PES1,PFKFB3,PHLDA2,PIM1,PINX1,PLK3,POP4,PPAN,PPP1R14A,HTRA2,OLA1,PTGES2,PTGS2,PTP4A3,PWP1,EPRS1,RASL11B,RBP4,PHB2,RERG,RGCC,RNASET2,RRP9,RPL10L,RPS27L,RRS1,UTP3,SAT1,SEC23B,SERPINH1,SGK1,SHMT1,SIX2,SLC12A3,SLC12A7,SLC16A6,SLC3A2,SNAI1,SRPRB,SSR1,STARD10,TAF9,KLF11,TOB1,TOMM20,TP53,TP53INP1,PDSS1,TSFM,TUBA8,TXNIP,VRK2,BUD23,WDR12,WRAP73,ZPR1,ZNF330,ZNF593,ZNF622 FOUNDER_NAMES