Promoter hypermethylation of the death-associated protein kinase gene in breast cancer is associated with the invasive lobular subtype.
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.
Lehmann
Ulrich
U
Institute of Pathology, Department of Pathology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany. Lehmann.Ulrich@MH-Hannover.de
Celikkaya
Gülhan
G
Hasemeier
Britta
B
Länger
Florian
F
Kreipe
Hans
H
D051017:Apoptosis Regulatory Proteins; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D064550:Death-Associated Protein Kinases; D020868:Gene Silencing; D006801:Humans; D006965:Hyperplasia / Q000201:enzymology / Q000235:genetics; D008198:Lymph Nodes / Q000201:enzymology / Q000502:physiology; D008214:Lymphocytes / Q000201:enzymology / Q000502:physiology; D009361:Neoplasm Invasiveness; D015203:Reproducibility of Results; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C000717967:DNMT3A protein, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases