title: Epigenetic alterations in sporadic basal cell carcinomas.
abstract: Basal cell carcinoma (BCC) is the most common malignant human neoplasm characterized by slow growth and virtual absence of metastases. Recently, it has become evident that along with genetic mutations epigenetic alterations play a key role in the pathogenesis of human cancer. We searched for promoter methylation of hMLH1, RASSF1A, DAPK, APC, DCR1 and DCR2 genes and BRAF mutations in BCCs in association with the clinicopathological parameters and the histological subtypes of the tumours. Fifty-two BCCs, 17 FFPE along with 35 fresh tissue samples with matching normal tissues for 26 cases were analyzed by methylation-specific PCR to assess the methylation status of hMLH1, RASSF1A, DAPK, APC, DCR1 and DCR2 genes after sodium bisulfite treatment of the tumour and normal DNA. hMLH1 and DCR1 gene expression was investigated by immunohistochemistry. BRAF mutations were studied by high resolution melting analysis. Methylation was detected at a variable frequency of 44, 33, 32.5, 32 and 14 % of DCR2, APC, DCR1, RASSF1 and DAPK promoters, respectively, whereas methylation of hMLH1 promoter was absent. No BRAF mutations were found. There was no correlation between the frequency of the promoter methylation of the above-mentioned genes and the clinicopathological features or the histological subtypes of the tumours. The relatively high frequency of RASSF1A, DCR1, DCR2 and APC promoter methylation may imply that methylation constitutes an important pathway in the tumourigenesis of BCC that could provide new opportunities in developing epigenetic therapies for BCC patients. Nevertheless, further studies are needed to establish the above-mentioned hypothesis.
authors.affiliation: 1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 11527, Athens, Greece, agstam@med.uoa.gr.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Stamatelli
authors.forename: Christina
authors.initials: C
authors.lastname: Vlachou
authors.forename: Kiriaki
authors.initials: K
authors.lastname: Aroni
authors.forename: Issidora
authors.initials: I
authors.lastname: Papassideri
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D012878:Skin Neoplasms / Q000235:genetics*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C555337:APC protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D058851:GPI-Linked Proteins; C501486:MLH1 protein, human; D009687:Nuclear 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; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1