TY - JOUR
T1 - Genetic determinants of malignancy in a mouse model for oligodendroglioma
AU - Weiss, William A.
AU - Burns, Michael J.
AU - Hackett, Christopher
AU - Aldape, Ken
AU - Hill, John R.
AU - Kuriyama, Hiroko
AU - Kuriyama, Nagato
AU - Milshteyn, Nadezhda
AU - Roberts, Tim
AU - Wendland, Michael F.
AU - DePinho, Ron
AU - Israel, Mark A.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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 S100β 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.
AB - 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 S100β 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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M3 - Article
C2 - 12670909
AN - SCOPUS:0037382205
SN - 0008-5472
VL - 63
SP - 1589
EP - 1595
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -