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Figure 3: Rate of Tumor Appearance in hi10 HeterozygotesA cohort of 28 hi10 fish and 13 of their noncarrier siblings were observed over 22 mo for the appearance of ill health or externally visible tumors. Symptomatic individuals were sacrificed, fixed, and sectioned for histological analysis. The graph represents the percentage of fish remaining over time, with the diagnosis of each removed fish. Three fish labeled “dead” died before fixation and had too much tissue damage to establish a diagnosis. Also, seven of the carrier fish (though none of the noncarriers) were lost to unknown causes over the course of the experiment; while they most likely died, to be conservative these were removed from the total number of fish charted. At 22 mo, the remaining externally healthy fish (4/21 carriers, 13/13 noncarriers) were also histologically examined, and the status of these fish is indicated.

Image Text (High Precision): MPNST carcinoma lymphoma months

Other Images from "Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish":


Figure 5 Ribosomal RNA Levels Are Reduced in RP M...

Figure 3 Rate of Tumor Appearance in hi10 Heteroz...

Figure 4 RP Genes Appear to Be Haploinsufficient ...

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Abstract

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and in some cases also other tumor types, with moderate to very high frequencies. Surprisingly, 11 of the 12 lines were each heterozygous for a mutation in a different ribosomal protein (RP) gene, while one line was heterozygous for a mutation in a zebrafish paralog of the human and mouse tumor suppressor gene, neurofibromatosis type 2. Our findings suggest that many RP genes may act as haploinsufficient tumor suppressors in fish. Many RP genes might also be cancer genes in humans, where their role in tumorigenesis could easily have escaped detection up to now.


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