DNA methylation patterns in genes implicated in ovarian cancer.
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- 作者：Killoran ; Kate A. ; Laprise ; Shari L. ; Patel ; Jay ; Weitzel ; Jeffrey N. ; Gray ; Mark R. ; Reindollar ; Richard H.
- 刊名：Journal of the Society for Gynecologic Investigation
- 出版年：1995
- 出版时间：March 4, 1995
- 年：1995
- 卷：2
- 期：2
- 页码：234
- 全文大小：106 K
文摘
The initial genetic event for cancer may be a mutation in one gene. Although some cases of cancer are associated with germline mutations, most are sporadic, and may be caused by somatic mutations. Somatic and germline mutations in genes encoding proteins that bind DNA, associate with the cytoskeleton, or mediate DNA repair have been implicated in the genesis of many different types of tumors. It remains difficult to identify the founder mutation for any tumor. The first mutation in the tumor pathway may create a permissive state for allowing new mutations in genes that regulate growth and differentiation. Changes in DNA methylation have been proposed to have a role in the primary tumor-causing genetic event. Aberrant DNA methylation has been shown to contribute to the formation of germline mutations in mammalian genes. The primary mutation that causes ovarian cancer may result in, or produce changes in DNA methylation. To test this hypothesis, DNA methylation patterns were compared in genes previously implicated in ovarian cancer. Denaturing gradient gel blots can detect any DNA modification that affects melting behavior. Tissue-specific melting polymorphisms are caused by methylation differences. Genomic DNA from different normal tissues, ovary, and ovarian tumors was digested with one of several restriction enzymes, electrophoresed in denaturing gradient gels, and transferred to nylon membranes. The blots were hybridized with probes made from eight different genes previously implicated in ovarian cancer. The candidate genes tested included both oncogenes and tumor suppressor genes. In contrast to genes that express high levels of tissue-specific products, very few methylation differences were found among DNA fragments from these loci. No tumor-specific methylation differences were detected. The results suggest that these candidate genes are similar to ubiquitously-expressed housekeeping genes, in having few methylation differences, and/or little methylation in any cell type. If DNA methylation has a major role in oncogenesis, differences most likely occur in genes other than those tested.