Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes

Cytogenetic, molecular genetic and functional analyses have implicated chromosome 3 genes in epithelial ovarian cancers (EOC). To further characterize their contribution to EOC, the Affymetrix U133A GeneChip((R)) was used to perform transcriptome analyses of chromosome 3 genes in primary cultures of normal ovarian surface epithelial (NOSE) cells (n = 14), malignant serous epithelial ovarian tumors (TOV) (n = 17), and four EOC cell lines (TOV-81D, TOV-112D, TOV-21G, and OV-90). A two-way comparative analysis of 735 known genes and expressed sequences identified 278 differentially expressed genes, where 43 genes were differentially expressed in at least 50% of the TOV samples. Three genes, R/S1 (at 3p2l.31), GBE1 (at 3p12.2), and HEG1 (at 3q21.2), were similarly underexpressed in all TOV samples. Deregulation of the expression of these genes was not associated with loss of heterozygosity (LOH) of the genetic loci harboring them. LOH analysis of the RIS1, GBE1, and HEG1 loci was observed at frequencies of 14.3%, 13.7%, and 9.2%, respectively, in a series of 66 malignant TOV samples of the serous subtype. Reduced expression levels of RIS1, GBE1, and HEG1 were observed only in the tumorigenic EOC cell lines (TOV-21G, TOV-112D, and OV-90) and did not correlate with LOH. These results combined suggest that RIS1, GBE1, and HEG1, unlike classical tumor suppressor genes, are not likely to be primary targets of inactivation. This study provides a comprehensive analysis of chromosome 3 gene expression in NOSE and in EOC samples and identifies chromosome 3 gene candidates for further study. (c) 2007 Wiley-Liss, Inc.