title: Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin.
abstract: BACKGROUND
  Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans.
  
  
  RESULTS
  We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples.
  
  
  CONCLUSIONS
  These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. aunterm1@jhmi.edu.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Vandiver
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. rafa@jimmy.harvard.edu.|Dana-Farber Cancer Institute, CLSB 11007, 450 Brookline Ave, Boston, MA, 02215, USA. rafa@jimmy.harvard.edu.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Irizarry
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. khansen@jhsph.edu.|Department of Biostatistics and Institute for Genetic Medicine, Johns Hopkins University School of Medicine, 615N. Wolfe St, E3527, Baltimore, MD, 21205, USA. khansen@jhsph.edu.
authors.forename: Kasper D
authors.initials: KD
authors.lastname: Hansen
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, CRB II Room 204, 1550 Orleans Street, Baltimore, MD, 21287, USA. LAG@jhmi.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Garza
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. arnirafn@gmail.com.
authors.forename: Arni
authors.initials: A
authors.lastname: Runarsson
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. xli81@jhmi.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, CRB II Room 204, 1550 Orleans Street, Baltimore, MD, 21287, USA. achien3@jhmi.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Chien
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, CRB II Room 204, 1550 Orleans Street, Baltimore, MD, 21287, USA. Twang49@jhmi.edu.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, CRB II Room 204, 1550 Orleans Street, Baltimore, MD, 21287, USA. sleung7@jhu.edu.
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Leung
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, CRB II Room 204, 1550 Orleans Street, Baltimore, MD, 21287, USA. swk@jhmi.edu.
authors.forename: Sewon
authors.initials: S
authors.lastname: Kang
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. afeinberg@jhu.edu.|Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. afeinberg@jhu.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D019175:DNA Methylation / Q000528:radiation effects; D004817:Epidermis / Q000378:metabolism*; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D015723:Gene Library; D023281:Genomics; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA; D015595:Skin Aging / Q000502:physiology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology; D013472:Sunlight / Q000009:adverse effects*