- Title
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Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish
- Authors
- Park, H., Galbraith, R., Turner, T., Mehojah, J., Azuma, M.
- Source
- Full text @ Sci. Rep.
Loss of ewsa promotes tumorigenesis. Total numbers of fish for each genotypes are: ewsaw/w;tp53w/w (n = 41), ewsaw/m;tp53w/w (n = 135), ewsam/m;tp53w/w (n = 21), ewsaw/w;tp53w/m (n = 28), ewsaw/m;tp53w/m (n = 46), ewsam/m;tp53w/m (n = 39), ewsaw/w;tp53m/m (n = 48), ewsaw/m;tp53m/m (n = 12), ewsam/m;tp53m/m (n = 19). (A) Representative images of zebrafish. In images of ewsa and tp53mutants, tumors are indicated with an arrow (>). Scale bar: 1cm. (B) Tumor incidence is higher in ewsaw/m;tp53w/m and ewsam/m;tp53w/m compared to ewsaw/w;tp53w/m; and in ewsaw/m;tp53m/m and ewsam/m;tp53m/m compared to ewsaw/w;tp53m/m zebrafish. (C) Average age at tumor onset is lower in ewsaw/m;tp53w/m and ewsam/m;tp53tp53w/m compared to ewsaw/w;tp53w/m; and in ewsaw/m;tp53m/m and ewsam/m;tp53m/m compared to ewsaw/w;tp53m/m zebrafish. (D) Representative images of H&E staining of tumors observed in zebrafish. MPNST-like: malignant peripheral nerve sheath tumor-like; SRBCT: small round blue cell tumor. |
Loss of ewsa promotes chromosomal instability (CIN). (A) Representative images of mitotic cells from 27 hours post fertilization (hpf) zebrafish embryos visualized by immunohistochemistry using an anti-α-tubulin antibody (red) and DAPI (blue). (B) Percentages of cells with aberrant mitosis in zebrafish embryos at 27 hours post fertilization, as determined after immunohistochemistry using an anti-α-tubulin antibody. Experiments were repeated three times. (n = 13 to 60 mitosis from 3 to 6 embryos per genotype). *P < 0.05. (C) Representative images of chromosomes obtained from metaphase spread of 24 hpf ewsaw/w (top) and MZ ewsam/m (bottom) embryos. (D) Numbers of chromosomes per cell, and percentage of cells from ewsaw/w (blue bars) and MZ ewsam/m (red bars) zebrafish embryos containing that number of chromosomes. The vast majority of ewsaw/w cells contained the normal chromosome number (50) (blue), whereas chromosome numbers in MZ ewsam/m mutant zebrafish cells varied from 34 to 56 chromosomes per cell (red). P < 0.05. Note that all samples were obtained from lines with wildtype tp53w/w background. PHENOTYPE:
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