Li Liming, Jiang Mingjun, Feng Qinghua, Kiviat Nancy B, Stern Joshua E, Hawes Stephen, Cherne Steve, Lu Hiep
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
Cell Biochem Biophys. 2015 Jun;72(2):599-604. doi: 10.1007/s12013-014-0507-2.
In order to elucidate the role of epigenetic alterations in the development of cutaneous squamous cell carcinoma (SCC), we analyzed both gene-specific promoter hypermethylation and repetitive sequence hypomethylation in cutaneous SCC as well as normal skin tissue samples. We showed that methylation of DAPK1 and CDH13 was associated with cutaneous SCC. While methylation frequency of DAPK1 was increased from sun-protected normal skin, sun-exposed normal skin, perilesional to lesional tissues, methylation of CDH13 was almost exclusively detected in cutaneous SCC tissues. Further, methylation of DAPK1 and CDH13 was neither correlated with the presence of HPV nor with the presence of p53 mutations in lesional skin tissues. Finally, we detected trend of reduced methylation level of repetitive sequences from sun-protected, sun-exposed normal skin samples to perilesional, and lesional tissues from SCC patients. We conclude that both gene-specific hypermethylation and repetitive sequence hypomethylation are present in cutaneous SCC tissue samples; these epigenetic changes might represent an independent pathway in the development of cutaneous SCC.
为了阐明表观遗传改变在皮肤鳞状细胞癌（SCC）发生发展中的作用，我们分析了皮肤SCC以及正常皮肤组织样本中基因特异性启动子高甲基化和重复序列低甲基化情况。我们发现，DAPK1和CDH13的甲基化与皮肤SCC相关。虽然DAPK1的甲基化频率从防晒正常皮肤、日晒正常皮肤、皮损周边组织到皮损组织逐渐升高，但CDH13的甲基化几乎仅在皮肤SCC组织中检测到。此外，DAPK1和CDH13的甲基化与皮损皮肤组织中HPV的存在以及p53突变均无关联。最后，我们检测到从防晒、日晒正常皮肤样本到皮损周边组织以及SCC患者的皮损组织，重复序列的甲基化水平有降低趋势。我们得出结论，皮肤SCC组织样本中存在基因特异性高甲基化和重复序列低甲基化；这些表观遗传变化可能代表了皮肤SCC发生发展中的一条独立途径。
