title: Aberrant DNA Methylation in Keratoacanthoma.
abstract: BACKGROUND
  Keratoacanthoma (KA) is a self-limiting epidermal tumor for which histopathological examination sometimes suggests malignancy. Based on inconsistent clinical views, KA can be regarded as both a benign tumor and a variant of squamous cell carcinoma (SCC). Aberrant DNA methylation frequently occurs in malignant tumors but it scarcely occurs in benign tumors. Whether aberrant methylation occurs in KA has not been previously examined.
  
  
  OBJECTIVE
  The aim is to elucidate whether aberrant methylation of CpG islands (CGI) containing a high density of cytosine-guanine dinucleotide (CpG) sites occurs in KA.
  
  
  METHODS
  Five SCC cell lines, two cultured samples of normal human epidermal keratinocytes (NHEKs), 18 clinical SCC samples, and 21 clinical KA samples were analyzed with Infinium HumanMethylation450 BeadChips, quantitative real-time methylation-specific PCR (RT-MSP) and/or bisulfite sequencing.
  
  
  RESULTS
  Genome-wide analyses of NHEK, KA, and SCC indicated that there was a greater number of aberrantly hypermethylated CGIs in SCC than in KA and there were aberrantly hypermethylated CGIs which are common in both. Among the common hypermethylated CGIs, RT-MSP and bisulfite sequencing targeting CGIs located on CCDC17, PVR, and MAP3K11 gene bodies also showed that methylation levels were significantly higher in KA than in normal epidermis. Statistical analyses suggested that the methylation level of CGI located on PVR in SCC might be correlated to lymph node metastasis (P = 0.013, Mann-Whitney U test) and that the methylation level of CGI in MAP3K11 in KA might be correlated to age (P = 0.031, linear regression analysis).
  
  
  CONCLUSIONS
  Aberrant DNA methylation occurs in KA.
authors: Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Yoshimasa
authors: http://orcid.org/0000-0002-0125-8930
authors: Y
authors: Nobeyama
authors: Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Hidemi
authors: H
authors: Nakagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D023281:Genomics; D006801:Humans; D007636:Keratoacanthoma / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged