Microarray comparative genomic hybridization profile of a murine model for epithelial ovarian cancer reveals genomic imbalances resembling human ovarian carcinomas.
Microarray comparative genomic hybridization (mCGH) is emerging as a high-resolution technology to detect gene dosage alterations in numerous pathologies, including cancer. We optimized cDNA microarrays to identify genome-wide imbalances in spontaneously transformed mouse ovarian surface epithelial cell lines, an in vitro murine model for ovarian cancer. Amplification of chromosome 19 and a more variable gain pattern of chromosomes 15 and 5 were detected and independently validated using conventional metaphase CGH. In addition, cryptic aberrations in segments of chromosomes 4, 7, 8, 9, 11, 17, and X, allowed identification of 2 related genomic variants among six cell lines studied. Mouse-human synteny revealed an overall early transformation stage with approximately 80% conservation relative to human ovarian malignancies of epithelial origin including low malignant potential tumors, serous carcinoma, and carcinoma cell lines. Importantly, three of the cells bear gained segments 13 and 41 Mbp length of chromosomes 5 and 15, respectively, which are syntenic to human 22q11-13, 8q24 and 12p11-q24, the two latter chromosomal regions thought to define one pathway of karyotypic changes in the development of human ovarian tumors. Our findings support the utility of mouse ovarian surface epithelial (MOSE) cells in studying initiation and progression of human ovarian cancer and as a suitable model to evaluate therapeutic approaches.
Urzua
Ulises
U
Laboratory of Molecular Technology, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA. uurzua@med.uchile.cl
Frankenberger
Casey
C
Gangi
Lisa
L
Mayer
Sara
S
Burkett
Sandra
S
Munroe
David J
DJ
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000662:veterinary*; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D004195:Disease Models, Animal; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D007621:Karyotyping; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000662:veterinary*; D014407:Tumor Cells, Cultured