title: Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients.
abstract: Despite the growing understanding of the mechanisms of carcinogenesis, cancers of the central nervous system are usually associated with unfavorable prognosis. The use of an appropriate molecular marker may improve the treatment outcome by allowing early diagnosis and treatment susceptibility monitoring. Since methylation of tumor-derived DNA can be detected in the serum of cancer patients, this makes DNA methylation-based biomarkers one of the most promising diagnostic strategies. In this study, the methylation profiles of MGMT, RASSF1A, p15INK4B, and p14ARF genes were evaluated in serum free-circulating DNA and the corresponding tumor tissue in a group of 33 primary or metastatic central nervous system cancer patients. Gene promoter methylation was assessed using methylation-specific polymerase chain reaction (PCR). All the tested genes were found to be methylated to a different extent in both serum and tumor samples. In comparison to metastatic brain tumor patients, the patients with glial tumors were characterized by a higher frequency of gene hypermethylation. The hypermethylation of RASSF1A differentiated primary from metastatic brain cancers. Moreover, the gene methylation profiles observed in serum, in most cases, matched the methylation profiles detected in paired tumor samples.
authors: Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, ul. Święcickiego 4, 60-781, Poznań, Poland.
authors: Aleksandra
authors: A
authors: Majchrzak-Celińska
authors: Jarosław
authors: J
authors: Paluszczak
authors: Robert
authors: R
authors: Kleszcz
authors: Marta
authors: M
authors: Magiera
authors: Anna-Maria
authors: AM
authors: Barciszewska
authors: Stanisław
authors: S
authors: Nowak
authors: Wanda
authors: W
authors: Baer-Dubowska
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000097:blood* / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
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