Many ribosomal protein genes are cancer genes in zebrafish

Adam Amsterdam, Kirsten C. Sadler, Kevin Lai, Sarah Farrington, Roderick T. Bronson, Jacqueline A. Lees, Nancy Hopkins

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalPLoS biology
Volume2
Issue number5
DOIs
StatePublished - 2004

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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    Amsterdam, A., Sadler, K. C., Lai, K., Farrington, S., Bronson, R. T., Lees, J. A., & Hopkins, N. (2004). Many ribosomal protein genes are cancer genes in zebrafish. PLoS biology, 2(5). https://doi.org/10.1371/journal.pbio.0020139