Systematic name M10828
Brief description 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].
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16150706   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
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Organism Danio rerio
Contributed by Jennifer Shepard (Broad Institute)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 7.3: Renamed from SHEPARD_CRUSH_AND_BURN_MUTANT_UP

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