title: Association of aberrant DNA methylation with clinicopathological features             in breast cancer.
abstract: Aberrant DNA methylation is responsible for the epigenetic silencing of             genes associated with tumourigenesis and progression of cancer. In this study,             we assessed the methylation status of eight genes in 49 snap-frozen primary breast             tumours. Epigenetic alterations of 8 genes were analysed with methylation-specific             polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or methylation-sensitive             high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1 and PTEN). MS-HRM             performance was validated by bisulfite pyrosequencing regarding the methylation             levels of MGMT. Promoter methylation was observed in APC 54.34%, 40.4% DCR1, 37.5%             DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0% DCR2 promoters,             respectively. Interestingly, 37 out of 49 cases (75.5%) displayed aberrant promoter             methylation in at least one gene. An association of MGMT promoter methylation             with age and tumour grade was recorded. Moreover, a correlation with advanced             T-category was elicited for GSTP1, RASSF1 and DAPK1 promoter methylation. Finally,             concurrent methylation of several genes showed a marginal statistical relationship             with N-category. We conclude that APC, DCR1, DAPK1 and RASSF1A promoter methylation             represents a common event in breast cancer tumourigenesis. Our results suggest             that GSTP1, RASSF1, DAPK1 and MGMT may be implicated in the acquisition of a more             aggressive phenotype in breast cancer.
authors.affiliation: First Department of Pathology, Medical School, National and Kapodistrian University of Athens, and First Propaedeutic Department of Surgery, Hippocration University Hospital, Athens, Greece. atserga@gmail.com
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Tserga
authors.forename: Nicolaos V
authors.initials: NV
authors.lastname: Michalopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: George
authors.initials: G
authors.lastname: Zografos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D044127:Epigenesis, Genetic; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; C411762:RASSF1 protein, human; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C108661:TNFRSF10C protein, human; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D025521:Tumor Suppressor Proteins; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases