Microarray Comparative Genomic Hybridization Profile of a Murine Model for Epithelial Ovarian Cancer Reveals Genomic Imbalances Resembling Human Ovarian Carcinomas

Vol. 26, No. 5, 2005

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Research Article

Microarray Comparative Genomic Hybridization Profile of a Murine Model for Epithelial Ovarian Cancer Reveals Genomic Imbalances Resembling Human Ovarian Carcinomas
Ulises Urzua^a, Casey Frankenberger^a, Lisa Gangi^a, Sara Mayer^a, Sandra Burkett^b, David J. Munroe^a

^aLaboratory of Molecular Technology and
^bLaboratory of Comparative Cytogenetics, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Md., USA

Address of Corresponding Author

Tumor Biol 2005;26:236-244 (DOI: 10.1159/000087378)

Key Words

DNA microarray
Ovarian cancer
Mouse model
Chromosomal aberrations

Abstract

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.

Author Contacts

Ulises Urzua
Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas
Facultad de Medicina, Universidad de Chile
Independencia 1027, Santiago 7 (Chile)
Tel. +56 2 678 6061, Fax +56 2 735 5580, E-Mail uurzua@med.uchile.cl

Article Information

Received: February 6, 2005
Accepted after revision: April 15, 2005
Published online: August 9, 2005
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 1, Number of References : 25

Medline Abstract (ID 16103745)

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