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Publication : Genetic determinants of malignancy in a mouse model for oligodendroglioma.

First Author  Weiss WA Year  2003
Journal  Cancer Res Volume  63
Issue  7 Pages  1589-95
PubMed ID  12670909 Mgi Jnum  J:82649
Mgi Id  MGI:2654313 Citation  Weiss WA, et al. (2003) Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res 63(7):1589-95
abstractText  Oligodendrogliomas of all grades overexpress epidermal growth factor receptor (EGFR), whereas deletion of ink4a/arf is found only in high-grade tumors. We used the S100 beta promoter to generate transgenic mice expressing v-erbB, a transforming allele of EGFR. These mice developed low-grade oligodendroglioma. Transgenic animals heterozygous for ink4a/arf or p53 developed high-grade tumors. Comparative genomic hybridization revealed loss of distal mouse chromosome 4, a region orthologous with human chromosome 1p, which is commonly lost in oligodendroglioma. Our results demonstrate that overexpression of EGFR, an epigenetic observation of uncertain significance in human oligodendroglioma, can initiate oligodendroglioma in the mouse. Furthermore, p53 pathway mutations can mediate the transition from low to high grade. These models hold promise for studying tumor lineage, identifying contributing genetic alterations and evaluating preclinical therapies in this important neoplasm.
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