Scientific Publications

A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility

Publication TypeJournal Article
AuthorsShepard, Jennifer L., Amatruda James F., Stern Howard M., Subramanian Aravind, Finkelstein David, Ziai James, Finley Rose K., Pfaff Kathleen L., Hersey Candace, Zhou Yi, Barut Bruce, Freedman Matthew, Lee Charles, Spitsbergen Jan, Neuberg Donna, and Weber Gerhard
AbstractA 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.
Year of Publication2005
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue37
Pages13194 - 9
Date Published (YYYY/MM/DD)2005/09/13/
ISBN Number0027-8424
KeywordsAnimals, Cancer, Cyclin B, Embryo, Genetic Predisposition to Disease, Genomic Instability, Mitosis, Mitotic Spindle Apparatus, Mutation, Neoplasms, Nonmammalian, Proto-Oncogene Proteins c-myb, Tumor Suppressor Protein p53, Zebrafish