Abstract
Expression of death-associated protein (DAP) kinase, a proapoptotic serine/threonine protein kinase, is frequently lost in human tumors. In a study of 134 primary breast cancer specimens hypermethylation of the DAP kinase gene was found in 13% of cases. A highly significant difference (P < 0.001) of DAP kinase inactivation was observed between invasive lobular cancer (n = 19) and invasive ductal cancer (n = 85; 53% versus 9%, respectively). Hypermethylation correlated with loss of RNA expression, estrogen receptor positivity (P < 0.01), and the absence of p53 overexpression (P < 0.01). In contrast to invasive lobular cancer, the in situ-growing precursor lesion lacked epigenetic modification of the DAP kinase promotor by aberrant methylation indicating a potential role in tumor progression. Unlike the DAP kinase gene, hypermethylation of the cyclin D2 and RASSF1A genes did not correlate with a particular histological subtype or to invasiveness [corrected]. We conclude that different histological subtypes of breast cancer may not only differ concerning specific chromosomal abnormalities and DNA mutations but also with regard to epigenetic inactivation patterns.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins
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Breast / pathology
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Breast Neoplasms / enzymology
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Breast Neoplasms / genetics*
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Breast Neoplasms / pathology
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Calcium-Calmodulin-Dependent Protein Kinases / genetics*
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Carcinoma, Intraductal, Noninfiltrating / enzymology
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Carcinoma, Intraductal, Noninfiltrating / genetics
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Carcinoma, Intraductal, Noninfiltrating / pathology
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Carcinoma, Lobular / enzymology
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Carcinoma, Lobular / genetics*
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Carcinoma, Lobular / pathology
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / biosynthesis
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DNA Methylation*
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DNA Methyltransferase 3A
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Death-Associated Protein Kinases
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Gene Silencing
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Humans
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Hyperplasia / enzymology
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Hyperplasia / genetics
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Lymph Nodes / enzymology
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Lymph Nodes / physiology
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Lymphocytes / enzymology
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Lymphocytes / physiology
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Neoplasm Invasiveness
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Reproducibility of Results
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Transcription, Genetic
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Tumor Cells, Cultured
Substances
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Apoptosis Regulatory Proteins
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DNMT3A protein, human
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNA Methyltransferase 3A
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Death-Associated Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases