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Genome-wide array CGH analysis of murine neuroblastoma reveals distinct genomic aberrations which parallel those in
Christopher S Hackett1, J Graeme Hodgson, Mark E Law
1Department of Neurology, University of California, San Francisco, California 94143-0114, USA.
Abstract:
Neuroblastoma, the third most common tumor of childhood, is a complex disease in which few genetic mutations have been identified.Mice expressing a human MYCN oncogene driven by the rat tyrosine hydroxylase promoter (TH-MYCN) represent an animal model for this disorder. We performed microarray-based comparative genomic hybridization analysis on murine tumors, identifying gains on chromosomes 1, 3, 11, 14, 17, and 18 and losses on chromosomes 5, 9, and 16. Fluorescence in situ hybridization analysis confirmed an amplicon on chromosome 18 as the site of TH-MYCN transgene integration. Selected tumors with localized gains of chromosome 11 delineate a 15-Mb region orthologous to human chromosome 17q and help to narrow the minimal region gained in human tumors. We observed clustered loss of chromosomes 5, 9, and 16, orthologous to a similar pattern of combined loss of chromosomes 3p, 4p, and 11q in human tumors. These data demonstrate conservation of many genetic changes in murine and human neuroblastoma and suggest that further delineation of genetic abnormalities in murine tumors may identify genes important in human disease.
Insights
This study analyzed genetic changes in a mouse model of neuroblastoma (NB), a common childhood cancer. Researchers identified conserved chromosomal gains and losses between mouse and human NB, suggesting this model can help discover new genes involved in NB development.
Area of Science:
- Oncology
- Genetics
- Comparative Genomics
Background:
- Neuroblastoma is a prevalent childhood cancer with limited identified genetic mutations.
- The TH-MYCN transgenic mouse model mimics human neuroblastoma, facilitating genetic studies.
- Understanding genetic alterations is crucial for advancing neuroblastoma research.
Purpose of the Study:
- To identify and characterize genetic abnormalities in the TH-MYCN mouse model of neuroblastoma.
- To compare genetic changes in the mouse model with those observed in human neuroblastoma.
- To leverage the mouse model for discovering genes implicated in neuroblastoma pathogenesis.
Main Methods:
- Microarray-based comparative genomic hybridization (aCGH) was employed to analyze murine tumors.
- Fluorescence in situ hybridization (FISH) was used to confirm transgene integration sites.
- Genomic data from mouse tumors were compared to known human neuroblastoma genetic alterations.
Main Results:
- aCGH revealed gains on chromosomes 1, 3, 11, 14, 17, and 18, and losses on chromosomes 5, 9, and 16 in murine tumors.
- FISH confirmed TH-MYCN transgene integration within an amplicon on chromosome 18.
- Gains on chromosome 11 in mice delineated a region orthologous to human chromosome 17q, and losses on chromosomes 5, 9, and 16 mirrored human chromosomal losses.
Conclusions:
- The TH-MYCN mouse model exhibits conserved genetic alterations with human neuroblastoma.
- These conserved changes suggest the mouse model is valuable for identifying genes driving neuroblastoma.
- Further investigation of murine genetic abnormalities may uncover critical genes for human neuroblastoma.
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