title: Genome-Wide Scan for Methylation Profiles in Keloids.
abstract: Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Lamont R
authors.initials: LR
authors.lastname: Jones
authors.affiliation: Proliance Eastside ENT, Kirkland, WA 98033, USA.
authors.forename: William
authors.initials: W
authors.lastname: Young
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA.
authors.forename: George
authors.initials: G
authors.lastname: Divine
authors.affiliation: Center for Bioinformatics, Henry Ford Health System, Detroit, MI 48202, USA.
authors.forename: Indrani
authors.initials: I
authors.lastname: Datta
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Kang Mei
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ozog
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Worsham
mesh_terms: D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007627:Keloid / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic