title: High frequency of DAP-kinase gene promoter methylation in colorectal cancer specimens and its identification in serum.
abstract: Death-associated protein (DAP)-kinase is frequently inactivated by promoter methylation in human cancers. To understand the involvement of the DAP-kinase gene in colorectal cancer (CRC), we investigated the methylation of the DAP-kinasegene in primary CRC to define the frequency of this epigenetic aberration and the clinicopathological significance. For this reason, methylation-specific polymerase chain reaction (MSP) was used to detect DAP-kinase gene methylation in DNA from 122 cases of CRC and 18 paired serum samples. Methylation of the DAP-kinase gene was found in 67 of 122 (55%) cases of primary CRC. Study of the serum DNA from 14 patients exhibiting methylated DAP-kinase gene revealed aberrant methylation in three patients (21%). False positives were not obtained in any of the patients who did not exhibit methylation. No association was found between the promoter methylation of the DAP-kinase gene in primary CRC and gender, localization, tumor differentiation, invasion depth, regional lymph node involvement, or tumor stage. In conclusion, methylation of the DAP-kinase gene is common in CRC. The detection of the methylation of the DAP-kinase gene has a potential clinical application as a diagnostic tumor marker for CRC.
authors.affiliation: First Department of Surgery, Gunma University Faculty of Medicine, 39-22, Showa-machi 3-chome, Maebashi, Gunma 371-8511, Japan. syamaguc@med.gunma-u.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nakamura
authors.forename: Munenori
authors.initials: M
authors.lastname: Ide
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013447:Sulfites / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D013447:Sulfites; D004247:DNA; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C009279:sodium bisulfite