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Epigenetic alterations in sporadic basal cell carcinomas

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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.

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Acknowledgments

The authors are grateful to PG Tsioli, S. Tsikalakis and I. Giannopoulou for performing experiments with the normal tissue specimens.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 11527, Athens, Greece

    Angeliki Stamatelli, Christina Vlachou, Kiriaki Aroni, Efstratios Patsouris & Angelica A. Saetta

  2. Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, 15784, Athens, Greece

    Issidora Papassideri

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  1. Angeliki Stamatelli
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  2. Christina Vlachou
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Correspondence to Angeliki Stamatelli.

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Stamatelli, A., Vlachou, C., Aroni, K. et al. Epigenetic alterations in sporadic basal cell carcinomas. Arch Dermatol Res 306, 561–569 (2014). https://doi.org/10.1007/s00403-014-1454-x

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  • DOI: https://doi.org/10.1007/s00403-014-1454-x

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