A cancer screen in zebrafish identifies many ribosomal proteins as haploinsufficient tumor suppressors

A collection of over 500 lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation caused by a retroviral insertion, was screened for lines that displayed early mortality and externally visible tumors. Among such tumor-prone lines identified was one in which the known human tumor suppressor gene, neurofibromatosis type 2 (NF2), was mutated. This validated the screening approach, as well as confirmed the human relevance of the zebrafish system in the study of cancer. Surprisingly, all of the remaining tumor-prone lines identified in the screen were ones in which a ribosomal protein (rp) gene was mutated. In total, 17 of 28 rp heterozygous lines were found to be predisposed to rare tumors, especially zebrafish malignant peripheral nerve sheath tumors (zMPNST). Though the precise molecular mechanism of tumorigenesis in rp heterozygous lines remains elusive, we have demonstrated that these rps are haploinsufficient tumor suppressors based on two lines of evidence: (1) The retroviral insertion causes a loss of function of the rp gene, as evidenced by a reduction in mRNA encoding the rp and a disruption of ribosomal integrity in the homozygous rp mutants;

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Lai, Kevin

Advisor dc:contributor.advisor

• Jacqueline A. Lees and Nancy Hopkins.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/35090
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/35090

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/35090