Promoter hypermethylation of the death-associated protein kinase gene in breast cancer is associated with the invasive lobular subtype.

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.

• Authors: Ulrich Lehmann, Gülhan Celikkaya, Britta Hasemeier, Florian Länger, Hans Kreipe
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 22 Pg. 6634-8 (Nov 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12438260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• DNMT3A protein, human
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• DNA Methyltransferase 3A
• Death-Associated Protein Kinases
• Calcium-Calmodulin-Dependent Protein Kinases

Topics

• Apoptosis Regulatory Proteins
• Breast (pathology)
• Breast Neoplasms (enzymology, genetics, pathology)
• Calcium-Calmodulin-Dependent Protein Kinases (genetics)
• Carcinoma, Intraductal, Noninfiltrating (enzymology, genetics, pathology)
• Carcinoma, Lobular (enzymology, genetics, pathology)
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (biosynthesis)
• DNA Methylation
• DNA Methyltransferase 3A
• Death-Associated Protein Kinases
• Gene Silencing
• Humans
• Hyperplasia (enzymology, genetics)
• Lymph Nodes (enzymology, physiology)
• Lymphocytes (enzymology, physiology)
• Neoplasm Invasiveness
• Reproducibility of Results
• Transcription, Genetic
• Tumor Cells, Cultured