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Methylation of Select Tumor Suppressor Genes in Sporadic Breast Cancer.

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Annual rept. 1 Jul 98-30 Jun 99

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The hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are likely to be tumor suppressor genes. It is through their loss of function that these genes confer a high-risk for developing the disease. Among a relatively large number of non-hereditary breast cancers that have been examined, BRCA1 and 2 mutations are very rare. Therefore, the conclusion has been made that these genes do not play a significant role in the more common sporadic forms of the disease. There are, however, other mechanisms besides mutations that can serve to inactivate the function of a gene. A common one is loss of expression due to hypermethylation of the associated CpG island. In this study, Dr. Magee measured the levels of BRCA1 and BRCA2 mRNA in an unselected set of 101 primary breast cancers and normal breast epithelial specimens. Dr. Magee found that these levels varied over a 20 fold range after normalization. In specimens that had very low levels of one or the other gene, the methylation status was examined to determine if a correlation existed between expression and hypermethylation. No correlation was found suggesting implying that the low levels of BRCA1 and 2 found in a subset of cancers is not due to aberrant methylation.

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  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

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