High resolution SNP array analysis of primary ovarian tumors reveals numerous microdeletions and amplifications.

A63

Genetic changes in sporadic ovarian cancer are poorly characterized. We have evaluated 31 primary ovarian cancers for loss of heterozygosity (LOH) and copy number alterations using the Affymetrix GeneChip® Mapping 500K Arrays. We analyzed DNA extracted from fresh frozen tumor and matching normal lymphocytes from 31 women with primary epithelial ovarian cancer, including three different histological subtypes - mucinous, endometrioid and serous. Analysis of the number of copy number breakpoints and the distribution of the small regions of copy number change indicate high levels of structural chromosomal genetic instability in ovarian cancer. There were differences in the number of chromosome breakpoints with tumor subtype, grade and stage. In addition to identifying the expected large-scale genomic copy number changes, the 500K array also revealed numerous smaller regions (<0.5 Mb) of high level amplification and homozygous loss in the tumor samples. Interestingly, several of these regions harbor genes with an unequivocal role in cancer development, for example RB1, raising the possibility that many of these regions will harbour novel ovarian cancer genes. The existence of such a high frequency of small regions exhibiting copy number alterations had not been previously suspected since earlier genomic array platforms lacked comparable resolution. In conclusion, the capability of high-resolution SNP arrays to identify very small genetic lesions will provide new powerful molecular approaches to the continued hunt for novel oncogenes and tumor suppressor genes.