title: DAPK1 promoter hypermethylaiton in brain metastases and peripheral blood.
abstract: The DAPK1 gene works as a regulator of apoptosis and is frequently inactivated in cancer by aberrant promoter hypermethylation. Loss of DAPK1 expression is associated with a selective advantage for tumor cells to resist apoptotic stimuli, allowing them to separate from the original tumor; from this point of view, DAPK1 could be considered a tumor metastases inhibitor gene. To verify the participation of DAPK1 silencing in cerebral invasion, we analyzed its promoter methylation status in a series of 28 samples from cerebral metastases using MSP and sequencing of the MSP-product. We have found hypermethylation in 53.6% (15/28) metastatic tumor samples as well as in 27.8% (5/18) of its peripheral blood samples. Our data suggest an important role of DAPK1 for silencing through promoter CpG island hypermethylation in the development of brain metastases from solid tumors. The detection of aberrant hypermethylation on DAPK1 promoter from peripheral blood samples has potential clinical implications as a tumor prognosis marker.
authors.affiliation: Unidad de Investigación, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Martinez-Glez
authors.forename: C
authors.initials: C
authors.lastname: Franco-Hernandez
authors.forename: P
authors.initials: P
authors.lastname: Gonzalez-Gomez
authors.forename: A
authors.initials: A
authors.lastname: Isla
authors.forename: J M
authors.initials: JM
authors.lastname: De Campos
authors.forename: J
authors.initials: J
authors.lastname: Vaquero
authors.forename: M
authors.initials: M
authors.lastname: Gutierrez
authors.forename: C
authors.initials: C
authors.lastname: Casartelli
authors.forename: J A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000097:blood* / Q000235:genetics*; D001374:Azacitidine / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics* / Q000556:secondary; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood* / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D064550:Death-Associated Protein Kinases; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001374:Azacitidine