Search for candidate ovarian tumor suppressor gene loci from a genomewide scan of ovarian cancers

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Several oncogenes and tumor suppressor genes including c-myc, c-erbB2/HER2/neu, K-ras, p53, Rb, PTEN, and BRCA1 genes are genetically altered in human ovarian cancers. Mutations of p53 gene have been detected with the incidence of 30-80%, however, genetic alterations in the other genes have been detected only in a small fraction of ovarian cancer. Identification of ovarian tumor suppressor gene is important for elucidation of ovarian cartinogenesis and development of gene therapy for ovarian cancer. To identify candidate ovarian tumor suppressor gene loci, we conducted a genomewide scan for regions of allelic loss using microdissected DNA from sporadic ovarian cancer patients.After signed informed consent was obtained, tumor and nontumor cells were laser capture microdissected (LCM) and genomic DNA was extracted from these cells. DNA from 98 ovarian cancers and corresponding normal tissue was analyzed for microsatellite alterations in 218 polymorphic markers covering all 22 autosomal chromosomes.In this study, the highest frequency of LOH on chromosome 17p was observed (74%). In addition, frequent losses (>50%) were observed on chromosome 5q, 5p, 8p, 13q, 14q, 14q, 17q, 18q, and 22q.Now we make the deletion map which is detail in human ovarian cancers and search for homozygous deletion in ovarian cancer cell lines on these chromosome arms.