PUBLICATION

Many ribosomal protein genes are cancer genes in zebrafish

Authors
Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S., Bronson, R.T., Lees, J.A., and Hopkins, N.
ID
ZDB-PUB-040514-5
Date
2004
Source
PLoS Biology   2(5): E139 (Journal)
Registered Authors
Amsterdam, Adam, Farrington, Sarah, Hopkins, Nancy, Sadler Edepli, Kirsten C.
Keywords
Tumor suppressor genes, Zebrafish, Point mutation, Suppressor genes, Histology, Embryos, Carcinogenesis, Insertion mutation
MeSH Terms
  • Animals
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Heterozygote
  • Humans
  • Loss of Heterozygosity
  • Mutagenesis
  • Mutation
  • Neurofibromin 2/genetics
  • Phenotype
  • RNA/chemistry
  • RNA, Ribosomal/chemistry
  • Ribosomal Proteins/chemistry*
  • Ribosomes/chemistry*
  • Zebrafish
PubMed
15138505 Full text @ PLoS Biol.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes