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Successful cell replication requires both cell cycle completion and accurate chromosomal segregation. The tumor suppressor BRCA2 is positioned to influence both of these outcomes, and thereby influence genomic integrity, during meiotic and mitotic cell cycles. Accordingly, mutations in  BRCA2  induce chromosomal abnormalities and disrupt cell cycle progression in both germ cells and somatic cells. Despite these findings, aneuploidy is not more prevalent in  BRCA2 -associated versus non- BRCA2 -associated human cancers. More puzzlingly, diploidy in  BRCA2 -associated cancers is a negative prognostic factor, unlike non- BRCA2 -associated cancers and many other human cancers. We used a  brca2 -mutant/ tp53 -mutant cancer-prone zebrafish model to explore the impact of  BRCA2  mutation on cell cycle progression, ploidy, and cancer-associated mortality by performing DNA content/cell cycle analysis on zebrafish germ cells, somatic cells, and cancer cells. First, we determined that combined  brca2/tp53  mutations uniquely disrupt meiotic progression. Second, we determined that sex significantly influences ploidy outcome in zebrafish cancers. Third, we determined that  brca2  mutation and female sex each significantly reduce survival time in cancer-bearing zebrafish. Finally, we provide evidence to support a link between  BRCA2  mutation, tumor diploidy, and poor survival outcome. These outcomes underscore the utility of this model for studying  BRCA2 -associated genomic aberrations in normal and cancer cells.

journal of oncology

Genotypic and Phenotypic Variables Affect Meiotic Cell Cycle Progression, Tumor Ploidy, and Cancer-Associated Mortality in a<i> brca2</i>-Mutant Zebrafish Model

Genotypic and Phenotypic Variables Affect Meiotic Cell Cycle Progression, Tumor Ploidy, and Cancer-Associated Mortality in a brca2-Mutant Zebrafish Model