title: Aberrant Methylation Changes Detected in Cutaneous Squamous Cell Carcinoma of Immunocompetent Individuals.
abstract: 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.
authors.affiliation: 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.
authors.forename: Liming
authors.initials: L
authors.lastname: Li
authors.affiliation: 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. drmingjunjiang@163.com.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA. drqinghuafeng@163.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Stern
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hawes
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Cherne
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Hiep
authors.initials: H
authors.lastname: Lu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007121:Immunocompetence; D008297:Male; D008875:Middle Aged; D012091:Repetitive Sequences, Nucleic Acid; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D015820:Cadherins; C099972:H-cadherin; D016159:Tumor Suppressor Protein p53; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases
keywords: CDH13; Cutaneous SCC tissues; DAPK1; Epigenetic alterations; Hypermethylation; Methylation; Squamous cell carcinoma (SCC)