DAP-kinase hypermethylation study in brain metastases of solid tumors.
aLab.Oncogenetica Molecular, Dpt. Cir. Experimental. Hospital Universitario La Paz, Madrid, Spain, bDpt. Genetica, Universidad de Sao Paolo. Riberao Preto, Brazil, cDpt. NeurocirugÃa, Hospital Universitario La Paz, Madrid, Spain, dDpt. NeurocirugÃa, Hospital del RÃo Hortega, Valladolid, Spain
AIM: Death-associated protein (DAP) kinase is a gene regulating apoptosis induced by INF-γ that is frequently inactivated by promoter hypermethylation in cancer. Loss of DAP-kinase expresion has been found to confer a relative advantage on tumor cells resistant to apoptotic stimuli, following their detachment from the original tumor and their transport in the circulation; thus DAP-kinase could be considered as a metastatic suppressor gene. METHODS: To verify the potential participation of DAP-kinase silencing in brain invasion, we analyzed the promoter methylation status of DAP-kinase in a series of 28 samples derived from brain metastases of solid tumors by methylation-specific PCR. The metastases were originated from: lung carcinoma (8 cases), malignant melanoma (7 cases), miosarcomas (4 cases), breast carcinoma (3 cases), ovarian carcinoma (2 cases), and one each from colon, kidney, bladder and undifferentiated carcinoma. RESULTS: Hypermethylation of DAP-kinase promoter was found in 15 metastases (54%) and in peripheral blood lymphocytes DNA from 5 of the 18 cases (44%) from which this non-tumoral DNA was disposable. CONCLUSIONS: Our data suggest an important role of the DAP-kinase promoter hypermethylation in brain metastases from solid tumors. The detection of aberrant promoter hypermethylation of the DAP-kinase gene in serum could have a potential clinical application as a diagnostic tumor marker for cancer cells.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).