Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification

MacPherson, D., Conkrite, K., Tam, M., Mukai, S., Mu, D., Jacks, T. (February 2007) Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification. Embo Journal, 26 (3). pp. 784-794. ISSN 0261-4189

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17235288
DOI: 10.1038/sj.emboj.7601515

Abstract

Human retinoblastoma is a pediatric cancer initiated by RB gene mutations in the developing retina. We have examined the origins and progression of retinoblastoma in mouse models of the disease. Retina-specific inactivation of Rb on a p130-/- genetic background led to bilateral retinoblastoma with rapid kinetics, whereas on a p107-/- background Rb mutation caused predominantly unilateral tumors that arose with delayed kinetics and incomplete penetrance. In both models, retinoblastomas arose from cells at the extreme periphery of the murine retina. Furthermore, late retinoblastomas progressed to invade the brain and metastasized to the cervical lymph nodes. Metastatic tumors lacking Rb and p130 exhibited chromosomal changes revealed by representational oligonucleotide microarray analysis including high-level amplification of the N-myc oncogene. N-myc was found amplified in three of 16 metastatic retinoblastomas lacking Rb and p130 as well as in retinoblastomas lacking Rb and p107. N-myc amplification ranged from 6- to 400-fold and correlated with high N-myc-expression levels. These murine models closely resemble human retinoblastoma in their progression and secondary genetic changes, making them ideal tools for further dissection of steps to tumorigenesis and for testing novel therapies.

Item Type: Paper
Uncontrolled Keywords: N-myc p107 p130 retinoblastoma ROMA COMPARATIVE GENOMIC HYBRIDIZATION OLIGONUCLEOTIDE MICROARRAY ANALYSIS RETINAL DEVELOPMENT CHIMERIC MICE MOUSE RETINA STEM-CELLS RB MUTATION P107 EXPRESSION
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > RB gene
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > retinoblastoma
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: CSHL Librarian
Date: February 2007
Date Deposited: 11 Nov 2011 16:16
Last Modified: 02 Apr 2018 16:14
PMCID: PMC1794380
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23089

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